M-6071-T-C

Variant names:

• chrM-6071-T-C
• rs7340086
• ENST00000361624.2:c.168T>C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_Strong BP7 BA1

The ENST00000361624.2(MT-CO1):​c.168T>C​(p.Val56Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.011 (AC: 653)
• Consequence: MT-CO1 ENST00000361624.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2 No linked disesase in Mitomap
• Conservation: PhyloP100: -10.7
• Publications: 3 publications found

Genes affected

MT-CO1 (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]

TRNC (HGNC:7477): (mitochondrially encoded tRNA cysteine)

TRNY (HGNC:7502): (mitochondrially encoded tRNA tyrosine)

TRNY Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP6: Variant M-6071-T-C is Benign according to our data. Variant chrM-6071-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 235696.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-10.7 with no splicing effect.
• BA1: High frequency in mitomap database: 0.0107

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COX1	unassigned_transcript_4799	c.168T>C	p.Val56Val	synonymous_variant	Exon 1 of 1
TRNC	unassigned_transcript_4797	c.-245A>G		upstream_gene_variant
TRNY	unassigned_transcript_4798	c.-180A>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-CO1	ENST00000361624.2	c.168T>C	p.Val56Val	synonymous_variant	Exon 1 of 1	6		ENSP00000354499.2
MT-TC	ENST00000387405.1	n.-245A>G		upstream_gene_variant		6
MT-TY	ENST00000387409.1	n.-180A>G		upstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.011 AC: 653

Gnomad homoplasmic AF: 0.027 AC: 1532 AN: 56414

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56414

Alfa AF: 0.00391 Hom.: 17

Mitomap

No disease associated.

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Aug 12, 2015

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

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 25, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-11
Mutation Taster		=74/26	polymorphism

Other links and lift over

dbSNP: rs7340086; hg19: chrM-6072;