rs118192103

Variant names:

• chrM-8342-G-A
• rs118192103
• unassigned_transcript_4803:c.48G>A

Your query was ambiguous. Multiple possible variants found:

• chrM-8342-G-A
• chrM-8342-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 0)
• Consequence: TRNK synonymous
• Scores: Mitotip Pathogenic 16
• Clinical Significance: Uncertain significance criteria provided, single submitter P:1 U:2 PEO-and-Myoclonus
• Conservation: PhyloP100: 0.0200

Genes affected

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

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]

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]

COX2 (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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRNK	unassigned_transcript_4803	c.48G>A	p.Glu16Glu	synonymous_variant	Exon 1 of 1
ATP6	unassigned_transcript_4805	c.-185G>A		upstream_gene_variant
ATP8	unassigned_transcript_4804	c.-24G>A		upstream_gene_variant
COX2	unassigned_transcript_4802	c.*73G>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD4 exome Cov.: 0

We have no GnomAD4 genomes data on this position. Probably position not covered by the project.

Mitomap GenBank AF: 0.0 AC: 0

Mitomap

PEO-and-Myoclonus

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1 Uncertain:2

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:2

May 04, 2022

Mendelics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 02, 2011

Stanford Center for Inherited Cardiovascular Disease, Stanford University

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. MT-TK m.8342G>A We classify it as a variant of uncertain significance. This variant has not been reported in association with cardiomyopathy in previous publications. It has been reported in association with an unspecified neuromuscular disorder. Tiranti et al (1999) describe an individual with muscle weakness, ophthalmoparesi s and this variant present with 80% heteroplasmy in muscle mtDNA and no heteroplasmy in lymphocyte DNA. The location of the nucleotide change is expected to alter the secondary structure of the resulting tRNA. A number of additional variants in this region of the MT-TK gene have been reported in association with mitochondrial disorders. This variant has not been reported in 6391 individuals at GeneDx, 2704 individuals in mtDB (www.genpath.uu.se/mtDB), 3735 individuals in MitoWheel (http://mitowheel.org/mitowheel.html). Triantis et al (1999) reported that m.8342G>A was not present in 100 presumably healthy controls. Thus in total this variant has not been detected in over 10,000 individuals. -

Progressive external ophthalmoplegia with myoclonus Pathogenic:1

Mar 01, 1999

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Pathogenic	16
Hmtvar	Pathogenic	0.65

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs118192103; hg19: chrM-8343;