rs118192103

Positions:

• chrM-8342-G-A

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:):

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/exons	MANE	Protein	UniProt
TRNK	unassigned_transcript_4804	c.48G>A	p.Glu16Glu	synonymous_variant	1/1
ATP8	unassigned_transcript_4805	c.-24G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	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

Uncertain significance, no assertion criteria provided	clinical testing	Stanford Center for Inherited Cardiovascular Disease, Stanford University	Dec 02, 2011	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. -
Uncertain significance, criteria provided, single submitter	clinical testing	Mendelics	May 04, 2022	- -

Progressive external ophthalmoplegia with myoclonus Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 01, 1999

- -

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;