rs1057520115

Variant names:

• chrM-8260-T-C
• rs1057520115
• ENST00000361739.1:c.675T>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP6_Moderate BP7 BS2

The ENST00000361739.1(MT-CO2):​c.675T>C​(p.Phe225Phe) 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 0.0011 (AC: 65)
• Consequence: MT-CO2 ENST00000361739.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -1.63
• 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]

MT-ATP8 (HGNC:7415): (mitochondrially encoded ATP synthase 8) Contributes to proton-transporting ATP synthase activity, rotational mechanism. Involved in mitochondrial ATP synthesis coupled proton transport. Part of mitochondrial proton-transporting ATP synthase complex. Implicated in multiple sclerosis and urinary bladder 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: Benign. The variant received -7 ACMG points.

• BP6: Variant M-8260-T-C is Benign according to our data. Variant chrM-8260-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 377045.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.63 with no splicing effect.
• BS2: High AC in GnomadMitoHomoplasmic at 123

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COX2	unassigned_transcript_4802	c.675T>C	p.Phe225Phe	synonymous_variant	Exon 1 of 1
ATP8	unassigned_transcript_4804	c.-106T>C		upstream_gene_variant
TRNK	unassigned_transcript_4803	c.-35T>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-CO2	ENST00000361739.1	c.675T>C	p.Phe225Phe	synonymous_variant	Exon 1 of 1	6		ENSP00000354876.1
MT-ATP8	ENST00000361851.1	c.-106T>C		upstream_gene_variant		6		ENSP00000355265.1
MT-TK	ENST00000387421.1	n.-35T>C		upstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.0011 AC: 65

Gnomad homoplasmic AF: 0.0022 AC: 123 AN: 56429

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56429

Alfa AF: 0.000894 Hom.: 4

Mitomap

No disease associated.

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 02, 2016

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

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.6
Mutation Taster		=99/1	polymorphism

Other links and lift over

dbSNP: rs1057520115; hg19: chrM-8261;