chrM-5979-G-A

Position:

• chrM-5979-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.00050 (AC: 32)
• Consequence: COX1 missense
• Scores: Apogee2 Benign 0.12
• Clinical Significance: Benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 9.63

Genes affected

COX1 (HGNC:7419): (mitochondrially encoded cytochrome c oxidase I) Contributes to cytochrome-c oxidase activity. Predicted to be involved in electron transport coupled proton transport and mitochondrial electron transport, cytochrome c to oxygen. Part of mitochondrial respiratory chain complex III and mitochondrial respiratory chain complex IV. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant M-5979-G-A is Benign according to our data. Variant chrM-5979-G-A is described in ClinVar as [Benign]. Clinvar id is 692604.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 31

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COX1	unassigned_transcript_4799	c.76G>A	p.Ala26Thr	missense_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	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: 0.00050 AC: 32

Gnomad homoplasmic AF: 0.00055 AC: 31 AN: 56394

Gnomad heteroplasmic AF: 0.00018 AC: 10 AN: 56394

Alfa AF: 0.000781 Hom.: 2

Mitomap

No disease associated.

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leigh syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

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

Oct 17, 2019

The NC_012920.1:m.5979G>A (YP_003024028.1:p.Ala26Thr) variant in MTCO1 gene is interpretated to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.12
Hmtvar	Pathogenic	0.73
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Uncertain	0.085	D
DEOGEN2	Benign	0.036	T
LIST_S2	Benign	0.80	T
MutationAssessor	Uncertain	2.7	M
PROVEAN	Benign	-1.2	N
Sift4G	Pathogenic	0.0010	D
GERP RS		5.3
Varity_R		0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1556423060; hg19: chrM-5980; COSMIC: COSV100677699; COSMIC: COSV100677699;