M-8839-G-C

Variant names:

• chrM-8839-G-C
• rs1556423547
• unassigned_transcript_4805:c.313G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Mitomap GenBank: Absent
• Consequence: ATP6 missense
• Scores: Apogee2 Pathogenic 0.93
• Clinical Significance: Pathogenic no assertion criteria provided P:1 O:1 NARP-syndrome
• Conservation: PhyloP100: 6.53

Genes affected

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: No frequency data in Mitomap. Probably very rare.
• PP5: Variant M-8839-G-C is Pathogenic according to our data. Variant chrM-8839-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 155892.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6	unassigned_transcript_4805	c.313G>C	p.Ala105Pro	missense_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD4 exome Cov.: 0

We have no GnomAD4 genomes data on this position. Probably position not covered by the project.

Mitomap

NARP-syndrome

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Mitochondrial disease Pathogenic:1

May 22, 2017

Wellcome Centre for Mitochondrial Research, Newcastle University

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Leigh syndrome Other:1

-

GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Pathogenic	0.93
Hmtvar	Pathogenic	0.90
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Uncertain	0.033	T
DEOGEN2	Benign	0.35	T
LIST_S2	Pathogenic	0.97	D
MutationAssessor	Pathogenic	4.9	H
PROVEAN	Pathogenic	-4.6	D
Sift4G	Pathogenic	0.0010	D
GERP RS		4.9
Varity_R		0.98

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1556423547; hg19: chrM-8840;