rs267606611

Variant names:

• chrM-9438-G-A
• rs267606611
• unassigned_transcript_4806:c.232G>A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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

• Frequency: Mitomap GenBank: 𝑓 0.012 (AC: 761)
• Consequence: COX3 missense
• Scores: Apogee2 Uncertain 0.44
• Clinical Significance: Benign criteria provided, single submitter P:1 B:1 LHON-/-gout
• Conservation: PhyloP100: 2.25

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 Benign. Variant got -10 ACMG points.

• BP6: Variant M-9438-G-A is Benign according to our data. Variant chrM-9438-G-A is described in ClinVar as [Benign]. Clinvar id is 9651.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: High frequency in mitomap database: 0.0124

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COX3	unassigned_transcript_4806	c.232G>A	p.Gly78Ser	missense_variant	Exon 1 of 1
ATP6	unassigned_transcript_4805	c.*231G>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: 0.012 AC: 761

Gnomad homoplasmic AF: 0.0034 AC: 192 AN: 56418

Gnomad heteroplasmic AF: 0.00011 AC: 6 AN: 56418

Alfa AF: 0.00233 Hom.: 11

Mitomap

LHON-/-gout

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leber optic atrophy Pathogenic:1

Oct 01, 1995

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Leigh syndrome Benign:1

Oct 17, 2019

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The NC_012920.1:m.9438G>A (YP_003024032.1:p.Gly78Ser) variant in MTCO3 gene is interpretated to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BA1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Uncertain	0.44
Hmtvar	Benign	0.27
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.30	T
DEOGEN2	Benign	0.11	T
LIST_S2	Benign	0.79	T
MutationAssessor	Uncertain	2.1	M
PROVEAN	Uncertain	-4.3	D
Sift	Benign	0.038	D
Sift4G	Uncertain	0.033	D
GERP RS		3.5
Varity_R		0.31

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs267606611; hg19: chrM-9439;