M-7598-G-A

Position:

• chrM-7598-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4 BP6_Moderate BA1

The ENST00000361739.1(MT-CO2):​c.13G>A​(p.Ala5Thr) 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 Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.010 (AC: 636)
• Consequence: MT-CO2 ENST00000361739.1 missense
• Scores: Apogee2 Benign 0.017
• Clinical Significance: Benign criteria provided, single submitter B:1 Possible-LHON-helper-variant
• Conservation: PhyloP100: -0.644

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]

MT-TD (HGNC:7478): (mitochondrially encoded tRNA aspartic acid)

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.016760925 < 0.5 .
• BP6: Variant M-7598-G-A is Benign according to our data. Variant chrM-7598-G-A is described in ClinVar as [Benign]. Clinvar id is 692748.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: High frequency in mitomap database: 0.0104

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COX2	COX2.1	c.13G>A	p.Ala5Thr	missense_variant	1/1		YP_003024029.1
TRND	TRND.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-CO2	ENST00000361739.1	c.13G>A	p.Ala5Thr	missense_variant	1/1			ENSP00000354876	P1
MT-TD	ENST00000387419.1			downstream_gene_variant

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap GenBank AF: 0.010 AC: 636

Gnomad homoplasmic AF: 0.0022 AC: 126 AN: 56397

Gnomad heteroplasmic AF: 0.00020 AC: 11 AN: 56397

Alfa AF: 0.00212 Hom.: 8

Mitomap

Possible-LHON-helper-variant

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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.7598G>A (YP_003024029.1:p.Ala4Thr) variant in MTCO2 gene is interpretated to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.017
Hmtvar	Benign	0.090
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.46	T
DEOGEN2	Benign	0.0057	T
LIST_S2	Benign	0.52	T
MutationAssessor	Benign	0.27	N
MutationTaster	Benign	1.0	N
PROVEAN	Benign	-0.14	N
Sift	Benign	0.35	T
Sift4G	Benign	0.40	T
GERP RS		-7.2
Varity_R		0.088

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs386420012; hg19: chrM-7599;