rs878853023

Positions:

• chrM-6120-A-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The ENST00000361624.2(MT-CO1):​c.217A>G​(p.Ile73Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 7/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I73T) has been classified as Uncertain significance.

• Frequency: Mitomap GenBank: 𝑓 0.00010 (AC: 9)
• Consequence: MT-CO1 ENST00000361624.2 missense
• Scores: Apogee2 Benign 0.018
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2 No linked disesase in Mitomap
• Conservation: PhyloP100: 3.30

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 Likely_benign. Variant got -5 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.018204905 < 0.5 .
• BS2: High AC in GnomadMitoHomoplasmic at 10

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COX1	COX1.1	c.217A>G	p.Ile73Val	missense_variant	1/1		YP_003024028.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-CO1	ENST00000361624.2	c.217A>G	p.Ile73Val	missense_variant	1/1			ENSP00000354499	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: 0.00010 AC: 9

Gnomad homoplasmic AF: 0.00018 AC: 10 AN: 56428

Gnomad heteroplasmic AF: 0.000089 AC: 5 AN: 56428

Mitomap

No disease associated.

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Leigh syndrome Uncertain:1

Uncertain significance, 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.6120A>G (YP_003024028.1:p.Ile73Val) variant in MTCO1 gene is interpretated to be a Uncertain Significance variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: no criteria -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Dec 22, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.018
Hmtvar	Pathogenic	0.61
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.37	T
DEOGEN2	Benign	0.015	T
LIST_S2	Benign	0.82	T
MutationAssessor	Benign	0.56	N
MutationTaster	Benign	1.0	N
PROVEAN	Benign	-0.50	N
Sift4G	Benign	0.19	T
GERP RS		5.1
Varity_R		0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs878853023; hg19: chrM-6121;