M-6060-A-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The ENST00000361624.2(MT-CO1):c.157A>C(p.Ile53Leu) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Mitomap GenBank: 𝑓 0.00010 (AC: 9)
• Consequence: MT-CO1 ENST00000361624.2 missense
• Scores: Apogee2 Benign 0.048
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 4.91

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 -1 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.048338283 < 0.5 .

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COX1	COX1.1	c.157A>C	p.Ile53Leu	missense_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-CO1	ENST00000361624.2	c.157A>C	p.Ile53Leu	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: 0.00010 AC: 9

Gnomad homoplasmic AF: 0.000035 AC: 2 AN: 56433

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56433

Mitomap

No disease associated.

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

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.6060A>C (YP_003024028.1:p.Ile53Leu) variant in MTCO1 gene is interpretated to be a Uncertain Significance variant based on the modified ACMG guidelines (unpublished).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: PP4, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.048
Hmtvar	Benign	0.14
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.55	T
DEOGEN2	Benign	0.017	T
LIST_S2	Benign	0.66	T
MutationAssessor	Benign	-0.090	N
MutationTaster	Benign	0.94	D
PROVEAN	Benign	-0.61	N
Sift4G	Benign	0.21	T
GERP RS		2.3
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: rs1603220250; hg19: chrM-6061;