chrM-9237-G-A

Position:

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP5_ModerateBP4

The ENST00000362079.2(MT-CO3):​c.31G>A​(p.Val11Met) variant causes a missense change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Mitomap GenBank:
𝑓 0.0 ( AC: 0 )

Consequence

MT-CO3
ENST00000362079.2 missense

Scores

Apogee2
Uncertain
0.46

Clinical Significance

Pathogenic criteria provided, single submitter P:2
Mitochondrial-Respiratory-Chain-Disorder

Conservation

PhyloP100: 9.47
Variant links:
Genes affected
MT-CO3 (HGNC:7422): (mitochondrially encoded cytochrome c oxidase III) Predicted to enable electron transfer activity and oxidoreduction-driven active transmembrane transporter activity. Involved in respiratory chain complex IV assembly. Part of respiratory chain complex IV. Implicated in MELAS syndrome. [provided by Alliance of Genome Resources, Apr 2022]
MT-ATP6 (HGNC:7414): (mitochondrially encoded ATP synthase 6) Contributes to proton-transporting ATP synthase activity, rotational mechanism. Involved in mitochondrial ATP synthesis coupled proton transport. Part of mitochondrial proton-transporting ATP synthase complex. Implicated in Leber hereditary optic neuropathy; NARP syndrome; Parkinson's disease; multiple sclerosis; and systemic lupus erythematosus. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very low frequency in mitomap database: 0.0
PP5
Variant M-9237-G-A is Pathogenic according to our data. Variant chrM-9237-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 370052.Status of the report is criteria_provided_single_submitter, 1 stars.
BP4
Apogee2 supports a benign effect, 0.45823577 < 0.5 .. Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COX3COX3.1 use as main transcriptc.31G>A p.Val11Met missense_variant 1/1 YP_003024032.1
ATP6ATP6.1 use as main transcript downstream_gene_variant YP_003024031.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MT-CO3ENST00000362079.2 linkuse as main transcriptc.31G>A p.Val11Met missense_variant 1/1 ENSP00000354982 P1
MT-ATP6ENST00000361899.2 linkuse as main transcript downstream_gene_variant ENSP00000354632 P1

Frequencies

GnomAD4 exome
Cov.:
0
We have no GnomAD4 genomes data on this position. Probably position not covered by the project.
Mitomap GenBank
AF:
0.0
AC:
0

Mitomap

Mitochondrial-Respiratory-Chain-Disorder

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Epilepsy;C0424605:Developmental delay;C1852373:Mitochondrial encephalopathy Pathogenic:1
Likely pathogenic, no assertion criteria providedclinical testingCenter for Neuroscience and Cell Biology, University of Coimbra, PortugalNov 21, 2016- -
Leber optic atrophy Pathogenic:1
Pathogenic, criteria provided, single submitterclinical testingMendelicsMay 04, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
Apogee2
Uncertain
0.46
Hmtvar
Pathogenic
0.57
AlphaMissense
Pathogenic
0.95
BayesDel_addAF
Benign
-0.11
T
DEOGEN2
Benign
0.030
T
LIST_S2
Uncertain
0.89
D
MutationAssessor
Pathogenic
3.3
M
MutationTaster
Benign
1.0
N
PROVEAN
Benign
-0.85
N
Sift
Pathogenic
0.0
D
GERP RS
5.0
Varity_R
0.60

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1057516064; hg19: chrM-9238; API