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

4640 (C > A)

General info

Mitimpact ID
MI.13113
Chr
chrM
Start
4640
Ref
C
Alt
A
Gene symbol
MT-ND2 Extended gene annotation
Gene position
171
Gene start
4470
Gene end
5511
Gene strand
+
Codon substitution
ATC/ATA
AA pos
57
AA ref
I
AA alt
M
Functional effect
missense
OMIM ID
516001
HGVS
NC_012920.1:g.4640C>A
HGNC ID
7456
RC complex
I
Ensembl gene ID
ENSG00000198763
Ensembl protein ID
ENSP00000355046
Ensembl transcript ID
ENST00000361453
Uniprot ID
P03891
Uniprot name
NU2M_HUMAN
Ncbi gene ID
4536
Ncbi protein ID
YP_003024027.1
Powered by NGL Viewer
Powered by MitoWheel

Conservation

PhyloP 100v
-9.187 Conservation Score
PhyloP 470way
-0.552 Conservation Score
PhastCons 100v
0 Conservation Score
PhastCons 470way
0.004 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
.
fathmm
.
AlphaMissense
Likely benign Score and details of the predictor
CADD
Deleterious Score and details of the predictor
PROVEAN
Tolerated Score and details of the predictor
Mutation Assessor
Neutral 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
Deleterious Score and details of the predictor
PANTHER
.
PhD-SNP
.

Pathogenicity meta-predictors

APOGEE1
Pathogenic Score and details of the meta-predictor
APOGEE2
Likely-benign 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
Neutral Score and details of the meta-predictor
MtoolBox
Deleterious Score and details of the meta-predictor
DEOGEN2
.
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
9718
Clinvar ALLELEID
24757
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
4640C>A
MITOMAP Disease Clinical info
Lhon / epilepsy
MITOMAP Disease Status
Reported
MITOMAP Disease Hom/Het
+/-
MITOMAP General GenBank Freq
0.3926%
MITOMAP General GenBank Seqs
240
MITOMAP General GenBank Curated refs
18676632 21145289 15972314 29987491 20301353 16523671 21457906 11479733
MITOMAP Variant Class
polymorphism;disease
Gnomad AN
56434
Gnomad AC hom
66
Gnomad AF hom
0.0011695
Gnomad AC het
0
Gnomad AF het
0.0
Gnomad filter
Pass
HelixMTdb AC hom
471
HelixMTdb AF hom
0.0024032
HelixMTdb AC het
4
HelixMTdb AF het
2.04e-05
HelixMTdb mean ARF
0.72782
HelixMTdb max ARF
0.91667
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
0.3 CPD variant frequency
AA ref
I
CPD AA alt
M
Aln pos
60
RefSeq protein ID
NP_072058 , YP_001876470
Species name
Echinops telfairi, Mus terricolor
Ncbi taxon ID
9371, 254704

4640 (C > G)

General info

Mitimpact ID
MI.13114
Chr
chrM
Start
4640
Ref
C
Alt
G
Gene symbol
MT-ND2 Extended gene annotation
Gene position
171
Gene start
4470
Gene end
5511
Gene strand
+
Codon substitution
ATC/ATG
AA pos
57
AA ref
I
AA alt
M
Functional effect
missense
OMIM ID
516001
HGVS
NC_012920.1:g.4640C>G
HGNC ID
7456
RC complex
I
Ensembl gene ID
ENSG00000198763
Ensembl protein ID
ENSP00000355046
Ensembl transcript ID
ENST00000361453
Uniprot ID
P03891
Uniprot name
NU2M_HUMAN
Ncbi gene ID
4536
Ncbi protein ID
YP_003024027.1
Powered by NGL Viewer
Powered by MitoWheel

Conservation

PhyloP 100v
-9.187 Conservation Score
PhyloP 470way
-0.552 Conservation Score
PhastCons 100v
0 Conservation Score
PhastCons 470way
0.004 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
Polymorphism Score and details of the predictor
fathmm
Tolerated Score and details of the predictor
AlphaMissense
Likely benign Score and details of the predictor
CADD
Deleterious Score and details of the predictor
PROVEAN
Tolerated Score and details of the predictor
Mutation Assessor
Neutral 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
Deleterious Score and details of the predictor
PANTHER
.
PhD-SNP
.

Pathogenicity meta-predictors

APOGEE1
Pathogenic Score and details of the meta-predictor
APOGEE2
Likely-benign 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
Neutral Score and details of the meta-predictor
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
4640C>G
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
.
~ 4640 (C/A) 4640 (C/G)
~ 4640 (ATC/ATA) 4640 (ATC/ATG)
MitImpact id MI.13113 MI.13114
Chr chrM chrM
Start 4640 4640
Ref C C
Alt A G
Gene symbol MT-ND2 MT-ND2
Extended annotation mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 2 mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 2
Gene position 171 171
Gene start 4470 4470
Gene end 5511 5511
Gene strand + +
Codon substitution ATC/ATA ATC/ATG
AA position 57 57
AA ref I I
AA alt M M
Functional effect general missense missense
Functional effect detailed missense missense
OMIM id 516001 516001
HGVS NC_012920.1:g.4640C>A NC_012920.1:g.4640C>G
HGNC id 7456 7456
Respiratory Chain complex I I
Ensembl gene id ENSG00000198763 ENSG00000198763
Ensembl transcript id ENST00000361453 ENST00000361453
Ensembl protein id ENSP00000355046 ENSP00000355046
Uniprot id P03891 P03891
Uniprot name NU2M_HUMAN NU2M_HUMAN
Ncbi gene id 4536 4536
Ncbi protein id YP_003024027.1 YP_003024027.1
PhyloP 100V -9.187 -9.187
PhyloP 470Way -0.552 -0.552
PhastCons 100V 0 0
PhastCons 470Way 0.004 0.004
PolyPhen2 possibly_damaging possibly_damaging
PolyPhen2 score 0.73 0.73
SIFT neutral neutral
SIFT score 0.2 0.2
SIFT4G Damaging Damaging
SIFT4G score 0.005 0.005
VEST Neutral Neutral
VEST pvalue 0.28 0.28
VEST FDR 0.45 0.45
Mitoclass.1 neutral neutral
SNPDryad Neutral Neutral
SNPDryad score 0.67 0.67
MutationTaster . Polymorphism
MutationTaster score . 1
MutationTaster converted rankscore . 0.08975
MutationTaster model . complex_aae
MutationTaster AAE . I57M
fathmm . Tolerated
fathmm score . 4.62
fathmm converted rankscore . 0.01834
AlphaMissense likely_benign likely_benign
AlphaMissense score 0.1618 0.1618
CADD Deleterious Deleterious
CADD score 3.484092 3.002618
CADD phred 23.1 22.2
PROVEAN Tolerated Tolerated
PROVEAN score -0.07 -0.07
MutationAssessor neutral neutral
MutationAssessor score -0.055 -0.055
EFIN SP Neutral Neutral
EFIN SP score 0.902 0.902
EFIN HD Neutral Neutral
EFIN HD score 0.65 0.65
MLC Deleterious Deleterious
MLC score 0.57064397 0.57064397
PANTHER score . .
PhD-SNP score . .
APOGEE1 Pathogenic Pathogenic
APOGEE1 score 0.57 0.53
APOGEE2 Likely-benign Likely-benign
APOGEE2 score 0.0832359133957599 0.0832359133957599
CAROL neutral neutral
CAROL score 0.85 0.85
Condel neutral neutral
Condel score 0.24 0.24
COVEC WMV neutral neutral
COVEC WMV score -3 -3
MtoolBox deleterious deleterious
MtoolBox DS 0.7 0.7
DEOGEN2 . Tolerated
DEOGEN2 score . 0.006266
DEOGEN2 converted rankscore . 0.05707
Meta-SNP . .
Meta-SNP score . .
PolyPhen2 transf low impact low impact
PolyPhen2 transf score -1.19 -1.19
SIFT_transf medium impact medium impact
SIFT transf score -0.13 -0.13
MutationAssessor transf medium impact medium impact
MutationAssessor transf score -0.69 -0.69
CHASM Neutral Neutral
CHASM pvalue 0.68 0.68
CHASM FDR 0.85 0.85
ClinVar id 9718.0 .
ClinVar Allele id 24757.0 .
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 LHON / Epilepsy .
MITOMAP Disease Status Reported .
MITOMAP Disease Hom/Het +/- ./.
MITOMAP General GenBank Freq 0.3926% .
MITOMAP General GenBank Seqs 240 .
MITOMAP General Curated refs 18676632;21145289;15972314;29987491;20301353;16523671;21457906;11479733 .
MITOMAP Variant Class polymorphism;disease .
gnomAD 3.1 AN 56434.0 .
gnomAD 3.1 AC Homo 66.0 .
gnomAD 3.1 AF Hom 0.00116951 .
gnomAD 3.1 AC Het 0.0 .
gnomAD 3.1 AF Het 0.0 .
gnomAD 3.1 filter PASS .
HelixMTdb AC Hom 471.0 .
HelixMTdb AF Hom 0.0024032698 .
HelixMTdb AC Het 4.0 .
HelixMTdb AF Het 2.0409934e-05 .
HelixMTdb mean ARF 0.72782 .
HelixMTdb max ARF 0.91667 .
ToMMo 54KJPN AC . .
ToMMo 54KJPN AF . .
ToMMo 54KJPN AN . .
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