rs1057516064

Variant names:

• chrM-9237-G-A
• rs1057516064
• unassigned_transcript_4806:c.31G>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 0)
• Consequence: COX3 missense
• Scores: Apogee2 Uncertain 0.46
• Clinical Significance: Pathogenic criteria provided, single submitter P:2 Mitochondrial-Respiratory-Chain-Disorder
• Conservation: PhyloP100: 9.47

Genes affected

COX3 (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]

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 4 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COX3	unassigned_transcript_4806	c.31G>A	p.Val11Ile	missense_variant	Exon 1 of 1
ATP6	unassigned_transcript_4805	c.*30G>A		downstream_gene_variant

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 GenBank AF: 0.0 AC: 0

Mitomap

Mitochondrial-Respiratory-Chain-Disorder

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Epilepsy;C0424605:Developmental delay;C1852373:Mitochondrial encephalopathy Pathogenic:1

Nov 21, 2016

Center for Neuroscience and Cell Biology, University of Coimbra, Portugal

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Leber optic atrophy Pathogenic:1

May 04, 2022

Mendelics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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
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

Other links and lift over

dbSNP: rs1057516064; hg19: chrM-9238;