Logo MitImpact
Home Description Output legend Molecular Dynamics How to cite License

4025 (C > T)

General info

Mitimpact ID
MI.12262
Chr
chrM
Start
4025
Ref
C
Alt
T
Gene symbol
MT-ND1 Extended gene annotation
Gene position
719
Gene start
3307
Gene end
4262
Gene strand
+
Codon substitution
ACA/ATA
AA pos
240
AA ref
T
AA alt
M
Functional effect
missense
OMIM ID
516000
HGVS
NC_012920.1:g.4025C>T
HGNC ID
7455
RC complex
I
Ensembl gene ID
ENSG00000198888
Ensembl protein ID
ENSP00000354687
Ensembl transcript ID
ENST00000361390
Uniprot ID
P03886
Uniprot name
NU1M_HUMAN
Ncbi gene ID
4535
Ncbi protein ID
YP_003024026.1
Powered by NGL Viewer
Powered by MitoWheel

Conservation

PhyloP 100v
-0.095 Conservation Score
PhyloP 470way
-0.552 Conservation Score
PhastCons 100v
0 Conservation Score
PhastCons 470way
0.001 Conservation Score

Pathogenicity predictors

PolyPhen2
Benign Score and details of the predictor
SIFT
Neutral Score and details of the predictor
SIFT4G
Damaging Score and details of the predictor
VEST
Neutral Score and details of the predictor
MitoClass 1
Neutral Score and details of the predictor
SNPDryad
Neutral Score and details of the predictor
MutationTaster
.
fathmm
.
AlphaMissense
Likely benign Score and details of the predictor
CADD
Neutral Score and details of the predictor
PROVEAN
Tolerated Score and details of the predictor
Mutation Assessor
.
EFIN SP
Neutral Score and details of the predictor
EFIN HD
Neutral Score and details of the predictor
MLC
Neutral Score and details of the predictor
PANTHER
.
PhD-SNP
.

Pathogenicity meta-predictors

APOGEE1
Neutral Score and details of the meta-predictor
APOGEE2
Benign Score and details of the meta-predictor
CAROL
Neutral Score and details of the meta-predictor
Condel
Deleterious Score and details of the meta-predictor
COVEC WMV
Neutral Score and details of the meta-predictor
MtoolBox
Neutral Score and details of the meta-predictor
DEOGEN2
.
Meta SNP
.

Cancer-specific predictors

PolyPhen2 transf
Medium impact Score and details of the cancer-specific predictor
SIFT transf
Medium impact Score and details of the cancer-specific predictor
MutationAssessor transf
Medium impact Score and details of the cancer-specific predictor
CHASM
Neutral Score and details of the cancer-specific predictor

Databases of Frequencies and Phenotypes

Clinvar ID
65520
Clinvar ALLELEID
76428
Clinvar CLNDISDB
Mondo:mondo:0009723, medgen:c0023264, omim:256000, orphanet:506;

human phenotype ontology:hp:0001086, human phenotype ontology:hp:0001112, mondo:mondo:0010788, medgen:c0917796, omim:535000, orphanet:104
Clinvar CLNDN
Leigh syndrome;

leber optic atrophy
Clinvar CLNSIG
Benign
MITOMAP Allele
4025C>T
MITOMAP Disease Clinical info
.
MITOMAP Disease Status
.
MITOMAP Disease Hom/Het
./.
MITOMAP General GenBank Freq
0.6919%
MITOMAP General GenBank Seqs
423
MITOMAP General GenBank Curated refs
11406419 21978175 21281460 7901141 8600429 17406640 24667788 11349229 7599218
MITOMAP Variant Class
polymorphism
Gnomad AN
56429
Gnomad AC hom
78
Gnomad AF hom
0.0013822
Gnomad AC het
3
Gnomad AF het
5.31e-05
Gnomad filter
Pass
HelixMTdb AC hom
379
HelixMTdb AF hom
0.0019338
HelixMTdb AC het
5
HelixMTdb AF het
2.55e-05
HelixMTdb mean ARF
0.58221
HelixMTdb max ARF
0.9
ToMMo JPN54K AC
7
ToMMo JPN54K AF
0.000129
ToMMo JPN54K AN
54302
COSMIC 90
.
dbSNP 156
.

Residue interaction

EVmutation
Site A-B InterP
Site A-B IntraP
ΔΔG intra
ΔΔG intra interface
ΔΔG inter

Compensated Pathogenic Deviations

Frequency
2.97 CPD variant frequency
AA ref
T
CPD AA alt
M
Aln pos
241
RefSeq protein ID
YP_161247 , NP_008225 , YP_659434 , YP_007024943 , YP_006460491 , YP_006460504 , YP_006460465 , YP_004425124 , YP_006460478 , YP_659473 , YP_004425111 , NP_007835 , YP_006883018 , YP_003587382 , YP_008379099 , NP_007822 , YP_003587214 , YP_003587279 , NP_008212 , YP_002120659
Species name
Notoryctes typhlops, Pongo pygmaeus, Semnopithecus entellus, Trachypithecus johnii, Rhinopithecus strykeri, Rhinopithecus bieti 2 rl-2012, Rhinopithecus brelichi, Rhinopithecus bieti, Rhinopithecus bieti 1 rl-2012, Rhinopithecus roxellana, Rhinopithecus avunculus, Pongo abelii, Nomascus gabriellae, Nomascus siki, Nomascus leucogenys, Hylobates lar, Hylobates agilis, Hylobates pileatus, Gorilla gorilla, Gorilla gorilla gorilla
Ncbi taxon ID
37699, 9600, 88029, 66063, 1194336, 1194335, 224329, 61621, 1194334, 61622, 66062, 9601, 61852, 9586, 61853, 9580, 9579, 9589, 9593, 9595

4025 (C > A)

General info

Mitimpact ID
MI.12261
Chr
chrM
Start
4025
Ref
C
Alt
A
Gene symbol
MT-ND1 Extended gene annotation
Gene position
719
Gene start
3307
Gene end
4262
Gene strand
+
Codon substitution
ACA/AAA
AA pos
240
AA ref
T
AA alt
K
Functional effect
missense
OMIM ID
516000
HGVS
NC_012920.1:g.4025C>A
HGNC ID
7455
RC complex
I
Ensembl gene ID
ENSG00000198888
Ensembl protein ID
ENSP00000354687
Ensembl transcript ID
ENST00000361390
Uniprot ID
P03886
Uniprot name
NU1M_HUMAN
Ncbi gene ID
4535
Ncbi protein ID
YP_003024026.1
Powered by NGL Viewer
Powered by MitoWheel

Conservation

PhyloP 100v
-0.095 Conservation Score
PhyloP 470way
-0.552 Conservation Score
PhastCons 100v
0 Conservation Score
PhastCons 470way
0.001 Conservation Score

Pathogenicity predictors

PolyPhen2
Possibly damaging Score and details of the predictor
SIFT
Neutral Score and details of the predictor
SIFT4G
Damaging Score and details of the predictor
VEST
Neutral Score and details of the predictor
MitoClass 1
Neutral Score and details of the predictor
SNPDryad
Neutral Score and details of the predictor
MutationTaster
Disease automatic Score and details of the predictor
fathmm
Tolerated Score and details of the predictor
AlphaMissense
Likely pathogenic Score and details of the predictor
CADD
Deleterious Score and details of the predictor
PROVEAN
Tolerated Score and details of the predictor
Mutation Assessor
Medium Score and details of the predictor
EFIN SP
Neutral Score and details of the predictor
EFIN HD
Neutral Score and details of the predictor
MLC
Neutral Score and details of the predictor
PANTHER
.
PhD-SNP
.

Pathogenicity meta-predictors

APOGEE1
Neutral Score and details of the meta-predictor
APOGEE2
Vus+ Score and details of the meta-predictor
CAROL
Neutral Score and details of the meta-predictor
Condel
Neutral Score and details of the meta-predictor
COVEC WMV
.
MtoolBox
Deleterious Score and details of the meta-predictor
DEOGEN2
Tolerated Score and details of the meta-predictor
Meta SNP
.

Cancer-specific predictors

PolyPhen2 transf
Low impact Score and details of the cancer-specific predictor
SIFT transf
Medium impact Score and details of the cancer-specific predictor
MutationAssessor transf
Medium impact Score and details of the cancer-specific predictor
CHASM
Neutral Score and details of the cancer-specific predictor

Databases of Frequencies and Phenotypes

Clinvar ID
.
Clinvar ALLELEID
.
Clinvar CLNDISDB
.
Clinvar CLNDN
.
Clinvar CLNSIG
.
MITOMAP Allele
4025C>A
MITOMAP Disease Clinical info
.
MITOMAP Disease Status
.
MITOMAP Disease Hom/Het
./.
MITOMAP General GenBank Freq
.
MITOMAP General GenBank Seqs
.
MITOMAP General GenBank Curated refs
.
MITOMAP Variant Class
.
Gnomad AN
0
Gnomad AC hom
0
Gnomad AF hom
0.0
Gnomad AC het
.
Gnomad AF het
.
Gnomad filter
.
HelixMTdb AC hom
0
HelixMTdb AF hom
0.0
HelixMTdb AC het
.
HelixMTdb AF het
0.0
HelixMTdb mean ARF
0.0
HelixMTdb max ARF
.
ToMMo JPN54K AC
.
ToMMo JPN54K AF
.
ToMMo JPN54K AN
.
COSMIC 90
.
dbSNP 156
.

Residue interaction

EVmutation
Site A-B InterP
Site A-B IntraP
ΔΔG intra
ΔΔG intra interface
ΔΔG inter

Compensated Pathogenic Deviations

Frequency
.
AA ref
.
CPD AA alt
.
Aln pos
.
RefSeq protein ID
.
Species name
.
Ncbi taxon ID
.
~ 4025 (C/T) 4025 (C/A)
~ 4025 (ACA/ATA) 4025 (ACA/AAA)
MitImpact id MI.12262 MI.12261
Chr chrM chrM
Start 4025 4025
Ref C C
Alt T A
Gene symbol MT-ND1 MT-ND1
Extended annotation mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1 mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1
Gene position 719 719
Gene start 3307 3307
Gene end 4262 4262
Gene strand + +
Codon substitution ACA/ATA ACA/AAA
AA position 240 240
AA ref T T
AA alt M K
Functional effect general missense missense
Functional effect detailed missense missense
OMIM id 516000 516000
HGVS NC_012920.1:g.4025C>T NC_012920.1:g.4025C>A
HGNC id 7455 7455
Respiratory Chain complex I I
Ensembl gene id ENSG00000198888 ENSG00000198888
Ensembl transcript id ENST00000361390 ENST00000361390
Ensembl protein id ENSP00000354687 ENSP00000354687
Uniprot id P03886 P03886
Uniprot name NU1M_HUMAN NU1M_HUMAN
Ncbi gene id 4535 4535
Ncbi protein id YP_003024026.1 YP_003024026.1
PhyloP 100V -0.095 -0.095
PhyloP 470Way -0.552 -0.552
PhastCons 100V 0 0
PhastCons 470Way 0.001 0.001
PolyPhen2 benign possibly_damaging
PolyPhen2 score 0.14 0.66
SIFT neutral neutral
SIFT score 0.91 0.14
SIFT4G Damaging Damaging
SIFT4G score 0.03 0.001
VEST Neutral Neutral
VEST pvalue 0.1 0.06
VEST FDR 0.4 0.35
Mitoclass.1 neutral neutral
SNPDryad Neutral Neutral
SNPDryad score 0.05 0.78
MutationTaster . Disease automatic
MutationTaster score . 8.60677e-18
MutationTaster converted rankscore . 0.08975
MutationTaster model . complex_aae
MutationTaster AAE . T240K
fathmm . Tolerated
fathmm score . 2.74
fathmm converted rankscore . 0.11730
AlphaMissense likely_benign likely_pathogenic
AlphaMissense score 0.141 0.8681
CADD Neutral Deleterious
CADD score 2.067474 2.627666
CADD phred 16.64 20.4
PROVEAN Tolerated Tolerated
PROVEAN score 0.09 -2.49
MutationAssessor . medium
MutationAssessor score . 3.025
EFIN SP Neutral Neutral
EFIN SP score 0.828 0.65
EFIN HD Neutral Neutral
EFIN HD score 0.782 0.43
MLC Neutral Neutral
MLC score 0.43149858 0.43149858
PANTHER score . .
PhD-SNP score . .
APOGEE1 Neutral Neutral
APOGEE1 score 0.24 0.41
APOGEE2 Benign VUS+
APOGEE2 score 0.0337449223449011 0.614343683689242
CAROL neutral neutral
CAROL score 0.06 0.87
Condel deleterious neutral
Condel score 0.89 0.24
COVEC WMV neutral .
COVEC WMV score -6 0
MtoolBox neutral deleterious
MtoolBox DS 0.15 0.52
DEOGEN2 . Tolerated
DEOGEN2 score . 0.200122
DEOGEN2 converted rankscore . 0.55760
Meta-SNP . .
Meta-SNP score . .
PolyPhen2 transf medium impact low impact
PolyPhen2 transf score -0.01 -1.02
SIFT_transf medium impact medium impact
SIFT transf score 0.84 -0.17
MutationAssessor transf medium impact medium impact
MutationAssessor transf score -0.25 1.34
CHASM Neutral Neutral
CHASM pvalue 0.59 0.49
CHASM FDR 0.8 0.8
ClinVar id 65520.0 .
ClinVar Allele id 76428.0 .
ClinVar CLNDISDB MONDO:MONDO:0009723,MedGen:C0023264,OMIM:256000,Orphanet:506|Human_Phenotype_Ontology:HP:0001086,Human_Phenotype_Ontology:HP:0001112,MONDO:MONDO:0010788,MedGen:C0917796,OMIM:535000,Orphanet:104 .
ClinVar CLNDN Leigh_syndrome|Leber_optic_atrophy .
ClinVar CLNSIG Benign .
MITOMAP Disease Clinical info . .
MITOMAP Disease Status . .
MITOMAP Disease Hom/Het ./. ./.
MITOMAP General GenBank Freq 0.6919% .
MITOMAP General GenBank Seqs 423 .
MITOMAP General Curated refs 11406419;21978175;21281460;7901141;8600429;17406640;24667788;11349229;7599218 .
MITOMAP Variant Class polymorphism .
gnomAD 3.1 AN 56429.0 .
gnomAD 3.1 AC Homo 78.0 .
gnomAD 3.1 AF Hom 0.00138227 .
gnomAD 3.1 AC Het 3.0 .
gnomAD 3.1 AF Het 5.31642e-05 .
gnomAD 3.1 filter PASS .
HelixMTdb AC Hom 379.0 .
HelixMTdb AF Hom 0.0019338412 .
HelixMTdb AC Het 5.0 .
HelixMTdb AF Het 2.5512418e-05 .
HelixMTdb mean ARF 0.58221 .
HelixMTdb max ARF 0.9 .
ToMMo 54KJPN AC 7 .
ToMMo 54KJPN AF 0.000129 .
ToMMo 54KJPN AN 54302 .
COSMIC 90 . .
dbSNP 156 id . .
For more info, please check the output legend.
ΔΔG values >±0.61 Kcal/mol are indicative of disrupting variants.
ΔΔG values close to zero (<±0.1 Kcal/mol) are indicative of possibly
compensating double mutants.
For more info, please check the output legend.
ΔΔG values >±0.61 Kcal/mol are indicative of disrupting variants.
ΔΔG values close to zero (<±0.1 Kcal/mol) are indicative of possibly
compensating double mutants.
For more info, please check the output legend.
ΔΔG values >±0.61 Kcal/mol are indicative of disrupting variants.
ΔΔG values close to zero (<±0.1 Kcal/mol) are indicative of possibly
compensating double mutants.
For more info, please check the output legend.
For more info, please check the output legend.
0
Details:
0
Score:  
0
  [min -20, max 10]
  • Predicted accelerated evolution:  score <= 0
  • Conserved:  score > 0
Score:  
0
  [min -20, max 12]
  • Predicted accelerated evolution:  score <= 0
  • Conserved:  score > 0
Score:  
0
  [min 0, max 1]
  • Non-conserved:  score <= 0.7
  • Conserved:  score > 0.7 (soft threshold)
Score:  
0
  [min 0, max 1]
  • Non-conserved:  score <= 0.7
  • Conserved:  score > 0.7 (soft threshold)
Score:  
0
  [min 0, max 1]
  • Neutral:  score <= 0.15
  • Possibly damaging:  0.15 < score <= 0.85
  • Probably damaging:  score > 0.85
Score:  
0
  [min 0, max 1]
  • Neutral:  score > 0.05
  • Deleterious:  score <= 0.05
Score:  
0
  [min 0, max 1]
  • Neutral:  score > 0.05
  • Deleterious:  score <= 0.05
Score:  
0
  [min -16.13, max 10.64]
  • Neutral:  score > 1.5
  • Deleterious:  score <= 1.5
Score:  
0
  [min 0.0, max 1.0]
  • Likely benign:  score <= 0.34
  • Ambiguous:  0.34 < score < 0.56
  • Likely pathogenic:  score >= 0.56
Score:  
0
  [min -14, max 14]
  • Neutral:  score > -2.5
  • Deleterious:  score <= -2.5 (soft threshold)
Score:  
0
  [min -6, max 6]
  • Neutral:  score <= 0.8
  • Low impact:  0.8 < score <= 1.9
  • Medium impact:  1.9 < score <= 3.5
  • High impact:  score > 3.5
Score:  
0
  [min 0, max 1]
  • Neutral:  score > 0.6
  • Damaging:  score <= 0.6
Score:  
0
  [min 0, max 1]
  • Neutral:  score > 0.28
  • Damaging:  score <= 0.28
Phred score:  
0
  [min 0, max Unlimited]
  • Neutral:  score < 20 (soft threshold)
  • Deleterious:  score >= 20
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5 (soft threshold)
  • Deleterious:  score >= 0.5
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5
  • Disease:  score >= 0.5
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5
  • Disease:  score >= 0.5
Score:  
0
  [min 0, max 1]
  • Polymorphism:  score < 0.5
  • Disease causing:  score >= 0.5
P-value:  
0
  [min 0, max 1]
  • Neutral:  p-value > 0.05
  • Pathogenic:  p-value <= 0.05
Score:  
0
  [min 0, max 1]
No hard-thresholds were indicated by authors (ref). Indicatively:
  • Neutral:  score < 0.9
  • Pathogenic:  score >= 0.9
No score. Categorical only
Please refer to Additional File 14: Table S10 for further details.
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.98
  • Deleterious:  score >= 0.98
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5
  • Disease:  score >= 0.5
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5
  • Deleterious:  score >= 0.5
Score:  
0
  [min -6, max 6]
  • Neutral:  score < 0
  • Deleterious:  score > 0
  • Inaccurate prediction:  score = 0
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5
  • Deleterious:  score >= 0.5
DS score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.43
  • Deleterious:  score >= 0.43
Pathogenicity score:  
0
  [min 0, max 1]
  • Neutral:  score ≤ 0.5
  • Pathogenic:  score > 0.5


Pathogenicity score for this variant:  
0
  [min 0, max 1]
ACMG-AMP curations for mitochondrial variants should use the raw scores. Standalone probabilities are shown below:
  • Benign:  score ≤ 0.062 (prob. ≤ 0.001)
  • Likely-benign:  0.062 < score ≤ 0.265 (0.001 < prob. ≤ 0.1)
  • Low-scoring VUS (VUS-):  0.265 < score ≤ 0.396 (0.1 < prob. ≤ 0.33)
  • VUS:  0.396 < score ≤ 0.544 (0.33 < prob. ≤ 0.66)
  • High-scoring VUS (VUS+):  0.544 < score < 0.716 (0.66 < prob. < 0.9)
  • Likely-pathogenic:  0.716 ≤ score < 0.907 (0.9 ≤ prob. < 0.99)
  • Pathogenic:  score ≥ 0.907 (prob. ≥ 0.99)
Score:  
0
  [min -5, max 5]
  • Low impact:  score <= -1 (soft threshold)
  • Medium impact:  -1 < score < 1.5 (soft threshold)
  • High impact:  score >= 1.5 (soft threshold)
Score:  
0
  [min -5, max 5]
  • Low impact:  score <= -1
  • Medium impact:  -1 < score < 2 (soft threshold)
  • High impact:  score >= 2 (soft threshold)
Score:  
0
  [min -5, max 5]
  • Low impact:  score <= -1
  • Medium impact:  -1 < score < 2 (soft threshold)
  • High impact:  score >= 2 (soft threshold)
P-value:  
0
  [min 0, max 1]
  • Neutral:  FDR > 0.2
  • Driver:  FDR <= 0.2
The frequency of a CPD variant is proportional to the
number of aligned orthologous sequences that
carry a specific human pathogenic variant as
wild-type amino acid on the total number of aligned
sequences.

For more info, please check the output legend