rs200715932

Variant names:

• chrM-8410-C-T
• rs200715932
• ENST00000361851.1:c.45C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP6_Very_Strong BP7 BS2

The ENST00000361851.1(MT-ATP8):​c.45C>T​(p.Pro15Pro) 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 0.0018 (AC: 109)
• Consequence: MT-ATP8 ENST00000361851.1 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2 No linked disesase in Mitomap
• Conservation: PhyloP100: -7.49
• Publications: 4 publications found

Genes affected

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]

MT-ATP6 (HGNC:7414): (mitochondrially encoded ATP synthase 6) 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 Leber hereditary optic neuropathy; NARP syndrome; Parkinson's disease; multiple sclerosis; and systemic lupus erythematosus. [provided by Alliance of Genome Resources, Apr 2022]

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: Benign. The variant received -13 ACMG points.

• BP6: Variant M-8410-C-T is Benign according to our data. Variant chrM-8410-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 235707.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-7.49 with no splicing effect.
• BS2: High AC in GnomadMitoHomoplasmic at 360

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP8	unassigned_transcript_4804	c.45C>T	p.Pro15Pro	synonymous_variant	Exon 1 of 1
ATP6	unassigned_transcript_4805	c.-117C>T		upstream_gene_variant
COX2	unassigned_transcript_4802	c.*141C>T		downstream_gene_variant
TRNK	unassigned_transcript_4803	c.*46C>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ATP8	ENST00000361851.1	c.45C>T	p.Pro15Pro	synonymous_variant	Exon 1 of 1	6		ENSP00000355265.1
MT-ATP6	ENST00000361899.2	c.-117C>T		upstream_gene_variant		6		ENSP00000354632.2
MT-CO2	ENST00000361739.1	c.*141C>T		downstream_gene_variant		6		ENSP00000354876.1
MT-TK	ENST00000387421.1	n.*46C>T		downstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.0018 AC: 109

Gnomad homoplasmic AF: 0.0064 AC: 360 AN: 56427

Gnomad heteroplasmic AF: 0.000089 AC: 5 AN: 56427

Alfa AF: 0.00359 Hom.: 17

Mitomap

No disease associated.

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Mar 18, 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		-7.5
Mutation Taster		=92/8	polymorphism

Other links and lift over

dbSNP: rs200715932; hg19: chrM-8411;