M-7650-C-T

Position:

• chrM-7650-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000361739.1(MT-CO2):​c.65C>T​(p.Thr22Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T22A) has been classified as Likely benign.

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 3)
• Consequence: MT-CO2 ENST00000361739.1 missense
• Scores: Apogee2 Benign 0.035
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 2.39

Genes affected

COX2 (HGNC:):

MT-CO2 (HGNC:7421): (mitochondrially encoded cytochrome c oxidase II) Contributes to cytochrome-c oxidase activity. Predicted to be involved in mitochondrial electron transport, cytochrome c to oxygen and positive regulation of vasoconstriction. Located in mitochondrial inner membrane. Part of respiratory chain complex IV. Biomarker of Huntington's disease and stomach cancer. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• BP4: Apogee2 supports a benign effect, 0.03450415 < 0.5 .

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COX2	COX2.1	c.65C>T	p.Thr22Ile	missense_variant	1/1		YP_003024029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-CO2	ENST00000361739.1	c.65C>T	p.Thr22Ile	missense_variant	1/1			ENSP00000354876	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: 0.0 AC: 3

Gnomad homoplasmic AF: 0.000053 AC: 3 AN: 56432

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56432

Alfa AF: 0.000223 Hom.: 1

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.7650C>T (YP_003024029.1:p.Thr22Ile) variant in MTCO2 gene is interpretated to be a Uncertain Significance variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.035
Hmtvar	Benign	0.17
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.38	T
DEOGEN2	Benign	0.022	T
LIST_S2	Benign	0.023	T
MutationAssessor	Benign	-0.55	N
MutationTaster	Benign	1.0	N
PROVEAN	Benign	-0.95	N
Sift	Benign	0.17	T
Sift4G	Uncertain	0.016	D
GERP RS		-0.78
Varity_R		0.080

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1603221063; hg19: chrM-7651;