M-7674-T-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4 BP6_Moderate BS2

The ENST00000361739.1(MT-CO2):c.89T>C(p.Ile30Thr) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I30V) has been classified as Likely benign.

• Frequency: Mitomap GenBank: 𝑓 0.00030 (AC: 16)
• Consequence: MT-CO2 ENST00000361739.1 missense
• Scores: Apogee2 Benign 0.16
• Clinical Significance: Likely benign criteria provided, single submitter B:1 O:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 3.98

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 Benign. Variant got -7 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.15822265 < 0.5 .
• BP6: Variant M-7674-T-C is Benign according to our data. Variant chrM-7674-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 692758.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 18

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COX2	COX2.1	c.89T>C	p.Ile30Thr	missense_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-CO2	ENST00000361739.1	c.89T>C	p.Ile30Thr	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: 0.00030 AC: 16

Gnomad homoplasmic AF: 0.00032 AC: 18 AN: 56427

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56427

Alfa AF: 0.000669 Hom.: 2

Mitomap

No disease associated.

ClinVar

Significance: Likely benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leigh syndrome Benign:1

Likely 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.7674T>C (YP_003024029.1:p.Ile30Thr) variant in MTCO2 gene is interpretated to be a Likely Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BS1, BP4, BP5 -

not provided Other:1

not provided, no classification provided

phenotyping only

GenomeConnect, ClinGen

-

Variant interpreted as Uncertain significance and reported on 05-04-2020 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.16
Hmtvar	Benign	0.24
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Benign	-0.23	T
DEOGEN2	Benign	0.15	T
LIST_S2	Benign	0.70	T
MutationAssessor	Pathogenic	3.3	M
MutationTaster	Benign	0.99	N
PROVEAN	Uncertain	-3.5	D
Sift	Benign	0.038	D
Sift4G	Uncertain	0.022	D
GERP RS		4.3
Varity_R		0.21

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1569484168; hg19: chrM-7675;