chrM-9545-A-G

Variant names:

• chrM-9545-A-G
• rs878853022
• ENST00000362079.2:c.339A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP6_Moderate BP7 BA1

The ENST00000362079.2(MT-CO3):​c.339A>G​(p.Gly113Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.046 (AC: 2796)
• Consequence: MT-CO3 ENST00000362079.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -5.39
• Publications: 4 publications found

Genes affected

MT-CO3 (HGNC:7422): (mitochondrially encoded cytochrome c oxidase III) Predicted to enable electron transfer activity and oxidoreduction-driven active transmembrane transporter activity. Involved in respiratory chain complex IV assembly. Part of respiratory chain complex IV. Implicated in MELAS syndrome. [provided by Alliance of Genome Resources, Apr 2022]

MT-CO3 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• hereditary recurrent myoglobinuria

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• cytochrome-c oxidase deficiency disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Leber hereditary optic neuropathy

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet
• Leigh syndrome

  Inheritance: Mitochondrial Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP6: Variant M-9545-A-G is Benign according to our data. Variant chrM-9545-A-G is described in ClinVar as Benign. ClinVar VariationId is 235374.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-5.39 with no splicing effect.
• BA1: High frequency in mitomap database: 0.045700002

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COX3	unassigned_transcript_4806	c.339A>G	p.Gly113Gly	synonymous_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-CO3	ENST00000362079.2	c.339A>G	p.Gly113Gly	synonymous_variant	Exon 1 of 1	6		ENSP00000354982.2

Frequencies

Mitomap GenBank AF: 0.046 AC: 2796

Gnomad homoplasmic AF: 0.021 AC: 1170 AN: 56414

Gnomad heteroplasmic AF: 0.000071 AC: 4 AN: 56414

Alfa AF: 0.00757 Hom.: 34

Mitomap

No disease associated.

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 17, 2015

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-5.4
Mutation Taster		=100/0	polymorphism

Other links and lift over

dbSNP: rs878853022; hg19: chrM-9546; COSMIC: COSV62294548; COSMIC: COSV62294548;