M-6054-G-A

Position:

• chrM-6054-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

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

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 0)
• Consequence: COX1 missense
• Scores: Apogee2 Benign 0.22
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 6.47

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COX1	unassigned_transcript_4799	c.151G>A	p.Asp51Asn	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: 0.0 AC: 0

Gnomad homoplasmic AF: 0.000018 AC: 1 AN: 56425

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56425

Mitomap

No disease associated.

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Mar 05, 2018

The m.6054G>A variant affected the MT-CO1 gene (c.151G>A; p.Asp51Asn) encoding the mitochondria cytochrome c oxidase I. This variant has not been reported in the medical literature and is not listed in gene-specific variant databases in association with disease. However, it is rare in the MITOMAP database (0.005% overall population frequency), and affects a highly conserved nucleotide and amino acid. Therefore, based on the available information, the clinical significance of the m.6054G>A variant cannot be determined with certainty. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.22
Hmtvar	Pathogenic	0.78
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Uncertain	0.11	D
DEOGEN2	Benign	0.082	T
LIST_S2	Pathogenic	0.98	D
MutationAssessor	Benign	1.8	L
PROVEAN	Uncertain	-3.0	D
Sift4G	Uncertain	0.010	D
GERP RS		5.1
Varity_R		0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1569484049; hg19: chrM-6055; COSMIC: COSV104668784; COSMIC: COSV104668784;