9185 (T > C)

General info

Chr
chrM
Start
9185
End
9185
Ref
T
Alt
C
Mitimpact ID
MI.1401
Gene symbol
MT-ATP6
RC complex
V
Ensembl gene ID
Ensembl protein ID
Ensembl transcript ID
Uniprot name
Uniprot ID
Ncbi gene ID
Ncbi protein ID
Gene position
659
AA pos
220
AA ref
L
AA alt
P
Codon substitution
cTc/cCc
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Conservation

PhyloP 100v
0.82 Conservation Score
PhastCons 100v
0.48 Conservation Score

Pathogenicity predictors

PolyPhen2
Probably damaging Score and details of the predictor
SIFT
Deleterious Score and details of the predictor
FatHmm
Deleterious Score and details of the predictor
FatHMMW
Neutral Score and details of the predictor
PROVEAN
Deleterious Score and details of the predictor
Mutation Assessor
High impact Score and details of the predictor
EFIN SP
Damaging Score and details of the predictor
EFIN HD
Neutral Score and details of the predictor
VEST
Neutral Score and details of the predictor
PANTHER
.
PhD-SNP
Disease Score and details of the predictor
MutationTaster
Disease causing automatic Score and details of the predictor
CADD
Deleterious Score and details of the predictor
SNAP
Disease Score and details of the predictor
MitoClass 1
Damaging Score and details of the predictor
SNPDryad
Pathogenic Score and details of the predictor

Pathogenicity meta-predictors

APOGEE
Likely-pathogenic Score and details of the meta-predictor
CAROL
Deleterious Score and details of the meta-predictor
Condel
Neutral Score and details of the meta-predictor
COVEC WMV
Deleterious Score and details of the meta-predictor
Meta SNP
Disease Score and details of the meta-predictor
MtoolBox
Deleterious Score and details of the meta-predictor
DEOGEN2
Neutral Score and details of the meta-predictor

Cancer-specific predictors

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

Databases of Phenotypes

ClinVar July2022 CLNSIG
Pathogenic
ClinVar July2022 CLNDN
Leber optic atrophy;

leigh syndrome;

charcot-marie-tooth disease;

mitochondrial complex 5 (atp synthase) deficiency, mitochondrial type 1;

mitochondrial disease;

not provided
ClinVar July2022 Variation ID
ClinVar July2022 CLNDISDB
Human phenotype ontology:hp:0001086, human phenotype ontology:hp:0001112, mondo:mondo:0010788, medgen:c0917796, omim:535000, orphanet:orpha104, snomed ct:58610003;

mondo:mondo:0009723, medgen:c0023264, omim:256000, orphanet:orpha506, snomed ct:29570005;

mondo:mondo:0015626, medgen:c0007959, omim:ps118220, orphanet:orpha166, snomed ct:50548001;

mondo:mondo:0027069, medgen:c3275684, omim:500015;

mondo:mondo:0044970, medgen:c0751651, orphanet:orpha68380;

medgen:cn517202
MITOMAP Allele
MITOMAP Disease Het/Hom
+/+
MITOMAP Disease Clinical info
Leigh disease / ataxia syndromes / narp-like disease / episodic weakness and charcot-marie-tooth
MITOMAP Disease Status
Cfrm
MITOMAP Disease GenBank Freq
0.000%
MITOMAP Disease GenBank Seqs
3 (0)
MITOMAP Disease GenBank Curated refs
34
MITOMAP General GenBank Freq
.
MITOMAP General GenBank Seqs
.
MITOMAP General GenBank Curated refs
.
Gnomad31 filter
Pass
Gnomad31 AC hom
0
Gnomad31 AC het
2
Gnomad31 AF hom
0
Gnomad31 AF het
3.5447792e-05
Gnomad31 AN
56421
HelixMTdb AC hom
0
HelixMTdb AF hom
0
HelixMTdb AC het
2
HelixMTdb AF het
1.0204967e-05
HelixMTdb mean ARF
0.43429
HelixMTdb max ARF
0.45192
COSMIC 90
.
dbSNP 155

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
.

9185 (T > G)

General info

Chr
chrM
Start
9185
End
9185
Ref
T
Alt
G
Mitimpact ID
MI.1402
Gene symbol
MT-ATP6
RC complex
V
Ensembl gene ID
Ensembl protein ID
Ensembl transcript ID
Uniprot name
Uniprot ID
Ncbi gene ID
Ncbi protein ID
Gene position
659
AA pos
220
AA ref
L
AA alt
R
Codon substitution
cTc/cGc
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Conservation

PhyloP 100v
0.82 Conservation Score
PhastCons 100v
0.48 Conservation Score

Pathogenicity predictors

PolyPhen2
Probably damaging Score and details of the predictor
SIFT
Deleterious Score and details of the predictor
FatHmm
Deleterious Score and details of the predictor
FatHMMW
Neutral Score and details of the predictor
PROVEAN
Deleterious Score and details of the predictor
Mutation Assessor
High impact Score and details of the predictor
EFIN SP
Damaging Score and details of the predictor
EFIN HD
Neutral Score and details of the predictor
VEST
Neutral Score and details of the predictor
PANTHER
.
PhD-SNP
Disease Score and details of the predictor
MutationTaster
Disease causing Score and details of the predictor
CADD
Deleterious Score and details of the predictor
SNAP
Disease Score and details of the predictor
MitoClass 1
Damaging Score and details of the predictor
SNPDryad
Pathogenic Score and details of the predictor

Pathogenicity meta-predictors

APOGEE
Vus Score and details of the meta-predictor
CAROL
Deleterious Score and details of the meta-predictor
Condel
Neutral Score and details of the meta-predictor
COVEC WMV
Deleterious Score and details of the meta-predictor
Meta SNP
Disease Score and details of the meta-predictor
MtoolBox
Deleterious Score and details of the meta-predictor
DEOGEN2
Neutral Score and details of the meta-predictor

Cancer-specific predictors

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

Databases of Phenotypes

ClinVar July2022 CLNSIG
.
ClinVar July2022 CLNDN
.
ClinVar July2022 Variation ID
ClinVar July2022 CLNDISDB
.
MITOMAP Allele
.
MITOMAP Disease Het/Hom
.
MITOMAP Disease Clinical info
.
MITOMAP Disease Status
.
MITOMAP Disease GenBank Freq
.
MITOMAP Disease GenBank Seqs
.
MITOMAP Disease GenBank Curated refs
.
MITOMAP General GenBank Freq
0.011%
MITOMAP General GenBank Seqs
6
MITOMAP General GenBank Curated refs
1
Gnomad31 filter
Pass
Gnomad31 AC hom
2
Gnomad31 AC het
1
Gnomad31 AF hom
3.5441513e-05
Gnomad31 AF het
1.7720757e-05
Gnomad31 AN
56431
HelixMTdb AC hom
15
HelixMTdb AF hom
7.653725e-05
HelixMTdb AC het
3
HelixMTdb AF het
1.530745e-05
HelixMTdb mean ARF
0.36981
HelixMTdb max ARF
0.85025
COSMIC 90
.
dbSNP 155

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
.

9185 (T > A)

General info

Chr
chrM
Start
9185
End
9185
Ref
T
Alt
A
Mitimpact ID
MI.1403
Gene symbol
MT-ATP6
RC complex
V
Ensembl gene ID
Ensembl protein ID
Ensembl transcript ID
Uniprot name
Uniprot ID
Ncbi gene ID
Ncbi protein ID
Gene position
659
AA pos
220
AA ref
L
AA alt
H
Codon substitution
cTc/cAc
Powered by NGL Viewer
Powered by MitoWheel

Conservation

PhyloP 100v
0.82 Conservation Score
PhastCons 100v
0.48 Conservation Score

Pathogenicity predictors

PolyPhen2
Probably damaging Score and details of the predictor
SIFT
Deleterious Score and details of the predictor
FatHmm
Deleterious Score and details of the predictor
FatHMMW
Neutral Score and details of the predictor
PROVEAN
Deleterious Score and details of the predictor
Mutation Assessor
High impact Score and details of the predictor
EFIN SP
Damaging Score and details of the predictor
EFIN HD
Neutral Score and details of the predictor
VEST
Neutral Score and details of the predictor
PANTHER
.
PhD-SNP
Disease Score and details of the predictor
MutationTaster
Disease causing Score and details of the predictor
CADD
Deleterious Score and details of the predictor
SNAP
Disease Score and details of the predictor
MitoClass 1
Damaging Score and details of the predictor
SNPDryad
Pathogenic Score and details of the predictor

Pathogenicity meta-predictors

APOGEE
Likely-pathogenic Score and details of the meta-predictor
CAROL
Deleterious Score and details of the meta-predictor
Condel
Neutral Score and details of the meta-predictor
COVEC WMV
Deleterious Score and details of the meta-predictor
Meta SNP
Disease Score and details of the meta-predictor
MtoolBox
Deleterious Score and details of the meta-predictor
DEOGEN2
Neutral Score and details of the meta-predictor

Cancer-specific predictors

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

Databases of Phenotypes

ClinVar July2022 CLNSIG
.
ClinVar July2022 CLNDN
.
ClinVar July2022 Variation ID
ClinVar July2022 CLNDISDB
.
MITOMAP Allele
.
MITOMAP Disease Het/Hom
.
MITOMAP Disease Clinical info
.
MITOMAP Disease Status
.
MITOMAP Disease GenBank Freq
.
MITOMAP Disease GenBank Seqs
.
MITOMAP Disease GenBank Curated refs
.
MITOMAP General GenBank Freq
0.002%
MITOMAP General GenBank Seqs
1
MITOMAP General GenBank Curated refs
1
Gnomad31 filter
.
Gnomad31 AC hom
.
Gnomad31 AC het
.
Gnomad31 AF hom
.
Gnomad31 AF het
.
Gnomad31 AN
.
HelixMTdb AC hom
.
HelixMTdb AF hom
.
HelixMTdb AC het
.
HelixMTdb AF het
.
HelixMTdb mean ARF
.
HelixMTdb max ARF
.
COSMIC 90
.
dbSNP 155

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
.
~ 9185 (T/C) 9185 (T/G) 9185 (T/A)
~ 9185 (cTc/cCc) 9185 (cTc/cGc) 9185 (cTc/cAc)
Chr chrM chrM chrM
Start 9185 9185 9185
End 9185 9185 9185
Ref T T T
Alt C G A
MitImpact id MI.1401 MI.1402 MI.1403
Gene symbol MT-ATP6 MT-ATP6 MT-ATP6
Respiratory Chain complex V V V
Ensembl gene id ENSG00000198899 ENSG00000198899 ENSG00000198899
Ensembl protein id ENSP00000354632 ENSP00000354632 ENSP00000354632
Ensembl transcript id ENST00000361899 ENST00000361899 ENST00000361899
Uniprot name ATP6_HUMAN ATP6_HUMAN ATP6_HUMAN
Uniprot id P00846 P00846 P00846
Ncbi gene id 4508 4508 4508
Ncbi protein id YP_003024031.1 YP_003024031.1 YP_003024031.1
Gene position 659 659 659
AA position 220 220 220
AA ref L L L
AA alt P R H
Codon substitution cTc/cCc cTc/cGc cTc/cAc
PhyloP 100V 0.82 0.82 0.82
PhastCons 100V 0.48 0.48 0.48
PolyPhen2 probably_damaging probably_damaging probably_damaging
PolyPhen2 score 1 1 1
SIFT deleterious deleterious deleterious
SIFT score 0 0 0
FatHmm deleterious deleterious deleterious
FatHmm score -4.18 -3.54 -4.12
FatHmmW neutral neutral neutral
FatHmmW score 4.08 4.09 4.08
PROVEAN deleterious deleterious deleterious
PROVEAN score -6.22 -5.32 -6.2
MutationAssessor high impact high impact high impact
MutationAssessor score 4.3 4.3 4.3
EFIN SP damaging damaging damaging
EFIN SP score 0.2 0.15 0.38
EFIN HD neutral neutral neutral
EFIN HD score 0.42 0.34 0.38
CADD deleterious deleterious deleterious
CADD score 3.99 4.32 4.22
CADD phred 23.6 24 23.9
VEST pvalue 0.2 0.19 0.22
VEST FDR 0.65 0.65 0.65
PANTHER . . .
PANTHER score . . .
PhD-SNP disease disease disease
PhD-SNP score 0.67 0.78 0.7
SNAP disease disease disease
SNAP score 0.76 0.77 0.73
Meta-SNP disease disease disease
Meta-SNP score 0.74 0.75 0.73
Meta-SNP RI 5 5 5
CAROL deleterious deleterious deleterious
CAROL score 1 1 1
Condel neutral neutral neutral
Condel score 0 0 0
COVEC WMV deleterious deleterious deleterious
COVEC WMV score 6 6 6
MtoolBox deleterious deleterious deleterious
MtoolBox DS 0.89 0.9 0.87
PolyPhen2 transf low impact low impact low impact
PolyPhen2 transf score -3.6 -3.6 -3.6
SIFT_transf low impact low impact low impact
SIFT transf score -1.4 -1.4 -1.4
MutationAssessor transf high impact high impact high impact
MutationAssessor transf score 2.59 2.59 2.59
CHASM pvalue 0.48 0.54 0.58
CHASM FDR 0.9 0.9 0.9
APOGEE Likely-pathogenic VUS Likely-pathogenic
APOGEE score 0.9045656434189292 0.5696993608763841 0.810281980867029
SNPDryad score 1 0.99 0.97
MutationTaster disease_causing_automatic disease_causing disease_causing
MutationTaster score 1 1 1
DEOGEN2 score 0.32 0.31 0.32
Mitoclass.1 damaging damaging damaging
dbSNP 155 id rs199476138 rs199476138 .
ClinVar October2021 Variation id 9647 . .
ClinVar October2021 CLNSIG Pathogenic . .
ClinVar October2021 CLNDN Leber_optic_atrophy|Leigh_syndrome|Charcot-Marie-Tooth_disease|Mitochondrial_complex_5_(ATP_synthase)_deficiency,_mitochondrial_type_1|Mitochondrial_disease|not_provided . .
ClinVar October2021 CLNDISDB Human_Phenotype_Ontology:HP:0001086,Human_Phenotype_Ontology:HP:0001112,MONDO:MONDO:0010788,MedGen:C0917796,OMIM:535000,Orphanet:ORPHA104,SNOMED_CT:58610003|MONDO:MONDO:0009723,MedGen:C0023264,OMIM:256000,Orphanet:ORPHA506,SNOMED_CT:29570005|MONDO:MONDO:0015626,MedGen:C0007959,OMIM:PS118220,Orphanet:ORPHA166,SNOMED_CT:50548001|MONDO:MONDO:0027069,MedGen:C3275684,OMIM:500015|MONDO:MONDO:0044970,MedGen:C0751651,Orphanet:ORPHA68380|MedGen:CN517202 . .
COSMIC 90 . . .
MITOMAP Allele T9185C . .
MITOMAP Disease Het/Hom +/+ . .
MITOMAP Disease Clinical info Leigh Disease / Ataxia syndromes / NARP-like disease / Episodic weakness and Charcot-Marie-Tooth . .
MITOMAP Disease Status Cfrm . .
MITOMAP Disease GenBank Freq 0.000% . .
MITOMAP Disease GenBank Seqs 3 (0) . .
MITOMAP Disease GenBank Curated refs 34 . .
MITOMAP General GenBank Freq . 0.011% 0.002%
MITOMAP General GenBank Seqs . 6 1
MITOMAP General Curated refs . 1 1
gnomAD 3.1 filter PASS PASS .
gnomAD 3.1 AC Homo 0 2 .
gnomAD 3.1 AC Het 2 1 .
gnomAD 3.1 AF Hom 0 3.5441513e-05 .
gnomAD 3.1 AF Het 3.5447792e-05 1.7720757e-05 .
gnomAD 3.1 AN 56421 56431 .
HelixMTdb AC Hom 0 15 .
HelixMTdb AF Hom 0 7.653725e-05 .
HelixMTdb AC Het 2 3 .
HelixMTdb AF Het 1.0204967e-05 1.530745e-05 .
HelixMTdb mean ARF 0.43429 0.36981 .
HelixMTdb max ARF 0.45192 0.85025 .
EVmutation MT-ATP6_220L|221Y:0.112703;222L:0.073089 MT-ATP6_220L|221Y:0.112703;222L:0.073089 MT-ATP6_220L|221Y:0.112703;222L:0.073089
Site A InterP . . .
Site B InterP . . .
Covariation Score InterP . . .
Site A IntraP . . .
Site B IntraP . . .
Covariation Score IntraP . . .
CPD AA ref . . .
CPD AA alt . . .
CPD Aln pos . . .
CPD Frequency . . .
CPD Species name . . .
CPD RefSeq Protein ID . . .
CPD Ncbi Taxon id . . .
DDG intra . . .
DDG intra interface . . .
DDG inter . . .
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.
Score:  
0
  [min -20, max 10]
  • Predicted accelerated evolution:  score <= 0
  • Conserved:  score > 0
Score:  
0
  [min 0, max 1]
  • Non-conserved:  score <= 0.9
  • Conserved:  score > 0.9 (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 -15, max 10]
  • Neutral:  score > -3
  • Deleterious:  score <= -3
Score:  
0
  [min -3, max 6]
  • Neutral:  score > -1.5
  • Deleterious:  score <= -1.5
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 35]
  • Neutral:  score < 20 (soft threshold)
  • Deleterious:  score >= 20
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]
  • 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 probability:  
0
  [min 0, max 1]
  • Benign:  probability ≤ 0.001
  • Likely-benign:  0.001 < probability ≤ 0.1
  • VUS:  0.1 < probability < 0.9
  • Likely-pathogenic:   0.9 ≤ probability < 0.99
  • Pathogenic:  probability ≥ 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