rs878853097

Variant names:

• chrM-8818-C-T
• rs878853097
• ENST00000361899.2:c.292C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_Strong BP7 BS1 BS2

The ENST00000361899.2(MT-ATP6):​c.292C>T​(p.Leu98Leu) 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 0.0065 (AC: 397)
• Consequence: MT-ATP6 ENST00000361899.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2 No linked disesase in Mitomap
• Conservation: PhyloP100: -0.115
• Publications: 4 publications found

Genes affected

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-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-ATP8 Gene-Disease associations (from GenCC):

• mitochondrial proton-transporting ATP synthase complex deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• periodic paralysis with later-onset distal motor neuropathy

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet
• mitochondrial disease

  Inheritance: AR, Mitochondrial Classification: LIMITED Submitted by: Illumina, ClinGen

ACMG classification

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

• BP6: Variant M-8818-C-T is Benign according to our data. Variant chrM-8818-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 235705.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.115 with no splicing effect.
• BS1: High frequency in mitomap database: 0.0064999997
• BS2: High AC in GnomadMitoHomoplasmic at 466

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6	unassigned_transcript_4805	c.292C>T	p.Leu98Leu	synonymous_variant	Exon 1 of 1
ATP8	unassigned_transcript_4804	c.*246C>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ATP6	ENST00000361899.2	c.292C>T	p.Leu98Leu	synonymous_variant	Exon 1 of 1	6		ENSP00000354632.2
MT-ATP8	ENST00000361851.1	c.*246C>T		downstream_gene_variant		6		ENSP00000355265.1

Frequencies

Mitomap GenBank AF: 0.0065 AC: 397

Gnomad homoplasmic AF: 0.0083 AC: 466 AN: 56431

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56431

Alfa AF: 0.00707 Hom.: 31

Mitomap

No disease associated.

ClinVar

Significance: Benign/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: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Jun 15, 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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.12

Other links and lift over

dbSNP: rs878853097; hg19: chrM-8819;