rs2248727

Variant names:

• chrM-9540-T-C
• rs2248727
• ENST00000362079.2:c.334T>C

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.334T>C​(p.Leu112Leu) 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 0.31 (AC: 19089)
• Consequence: MT-CO3 ENST00000362079.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2 No linked disesase in Mitomap
• Conservation: PhyloP100: -1.96
• Publications: 16 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-9540-T-C is Benign according to our data. Variant chrM-9540-T-C is described in ClinVar as [Benign]. Clinvar id is 3027421.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.96 with no splicing effect.
• BA1: High frequency in mitomap database: 0.31219998

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COX3	unassigned_transcript_4806	c.334T>C	p.Leu112Leu	synonymous_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-CO3	ENST00000362079.2	c.334T>C	p.Leu112Leu	synonymous_variant	Exon 1 of 1	6		ENSP00000354982.2

Frequencies

Mitomap GenBank AF: 0.31 AC: 19089

Gnomad homoplasmic AF: 0.30 AC: 17141 AN: 56323

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56323

Alfa AF: 0.192 Hom.: 8465

Mitomap

No disease associated.

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Venous thromboembolism Benign:1

-

Genomics Division, Defence Institute of Physiology and Allied Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: case-control

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.0
Mutation Taster		=36/64	disease causing

Other links and lift over

dbSNP: rs2248727; hg19: chrM-9541; COSMIC: COSV104419768; COSMIC: COSV104419768;