rs386829022

Variant names:

• chrM-8047-T-C
• rs386829022
• ENST00000361739.1:c.462T>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP7 BS2

The ENST00000361739.1(MT-CO2):​c.462T>C​(p.Ile154Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Mitomap GenBank: 𝑓 0.0010 (AC: 62)
• Consequence: MT-CO2 ENST00000361739.1 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -5.89
• Publications: 1 publications found

Genes affected

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]

TRNK (HGNC:7489): (mitochondrially encoded tRNA lysine)

TRNK Gene-Disease associations (from GenCC):

• Leigh syndrome

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• maternally-inherited cardiomyopathy and hearing loss

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

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP7: Synonymous conserved (PhyloP=-5.89 with no splicing effect.
• BS2: High AC in GnomadMitoHomoplasmic at 57

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361739.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-CO2	ENST00000361739.1	TSL:6	c.462T>C	p.Ile154Ile	synonymous	Exon 1 of 1	ENSP00000354876.1
	MT-TK	ENST00000387421.1	TSL:6	n.-248T>C		upstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.0010 AC: 62

Gnomad homoplasmic AF: 0.0010 AC: 57 AN: 56428

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56428

Alfa AF: 0.000111 Hom.: 0

Mitomap

No disease associated.

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-5.9
Mutation Taster		=71/29	polymorphism

Other links and lift over

dbSNP: rs386829022; hg19: chrM-8048;