rs201262114

Positions:

• chrM-6261-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4 BP6_Very_Strong BS1 BS2

The ENST00000361624.2(MT-CO1):​c.358G>A​(p.Ala120Thr) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.0081 (AC: 496)
• Consequence: MT-CO1 ENST00000361624.2 missense
• Scores: Apogee2 Benign 0.093
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3 Prostate-Cancer-/-LHON
• Conservation: PhyloP100: 7.69

Genes affected

COX1 (HGNC:):

MT-CO1 (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 Benign. Variant got -17 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.09348247 < 0.5 .
• BP6: Variant M-6261-G-A is Benign according to our data. Variant chrM-6261-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 235718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: High frequency in mitomap database: 0.0081
• BS2: High AC in GnomadMitoHomoplasmic at 401

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COX1	COX1.1	c.358G>A	p.Ala120Thr	missense_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-CO1	ENST00000361624.2	c.358G>A	p.Ala120Thr	missense_variant	1/1			P1

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap GenBank AF: 0.0081 AC: 496

Gnomad homoplasmic AF: 0.0071 AC: 401 AN: 56365

Gnomad heteroplasmic AF: 0.00018 AC: 10 AN: 56365

Alfa AF: 0.0112 Hom.: 260

Mitomap

Prostate-Cancer-/-LHON

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 15, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 16, 2019	- -

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.6261G>A (YP_003024028.1:p.Ala120Thr) 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: BA1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.093
Hmtvar	Pathogenic	0.66
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.43	T
DEOGEN2	Benign	0.0058	T
LIST_S2	Benign	0.71	T
MutationAssessor	Benign	0.47	N
MutationTaster	Benign	0.91	D
PROVEAN	Benign	0.27	N
Sift4G	Benign	0.12	T
GERP RS		4.5
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: rs201262114; hg19: chrM-6262;