M-7649-A-G

Variant names:

• chrM-7649-A-G
• rs1603221060
• unassigned_transcript_4802:c.64A>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP6_Moderate BS2

In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 2)
• Consequence: COX2 missense
• Scores: Apogee2 Benign 0.030
• Clinical Significance: Likely benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -0.372

Genes affected

COX2 (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]

TRNS1 (HGNC:7497): (mitochondrially encoded tRNA serine 1 (UCN))

COX1 (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]

TRND (HGNC:7478): (mitochondrially encoded tRNA aspartic acid)

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• BP6: Variant M-7649-A-G is Benign according to our data. Variant chrM-7649-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 692753.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 10

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COX2	unassigned_transcript_4802	c.64A>G	p.Thr22Ala	missense_variant	Exon 1 of 1
TRNS1	unassigned_transcript_4800	c.-135T>C		upstream_gene_variant
COX1	unassigned_transcript_4799	c.*204A>G		downstream_gene_variant
TRND	unassigned_transcript_4801	c.*64A>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

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: 2

Gnomad homoplasmic AF: 0.00018 AC: 10 AN: 56429

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56429

Mitomap

No disease associated.

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leigh syndrome Benign:1

Oct 17, 2019

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The NC_012920.1:m.7649A>G (YP_003024029.1:p.Thr22Ala) 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: BS4, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.030
Hmtvar	Benign	0.12
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.44	T
DEOGEN2	Benign	0.0049	T
LIST_S2	Benign	0.012	T
MutationAssessor	Benign	-0.83	N
PROVEAN	Benign	-0.010	N
Sift	Benign	0.20	T
Sift4G	Benign	0.097	T
GERP RS		-7.5
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: rs1603221060; hg19: chrM-7650;