ENST00000362079.2:c.334T>C

Variant names:

• chrM-9540-T-C
• rs2248727
• ENST00000362079.2:c.334T>C
• MT-CO3 p.Leu112Leu

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 VariationId 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000362079.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-CO3	ENST00000362079.2	TSL:6	c.334T>C	p.Leu112Leu	synonymous	Exon 1 of 1	ENSP00000354982.2	P00414

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)
-	-	1	Venous thromboembolism (1)

Computational scores

Source: dbNSFP v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2248727;

hg19: chrM-9541;

COSMIC: COSV104419768;

COSMIC: COSV104419768;