rs118192103

chrM-8342-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The ENST00000387421.1(MT-TK):n.48G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 0)
• Consequence: MT-TK ENST00000387421.1 non_coding_transcript_exon
• 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

MT-TK (HGNC:7489): (mitochondrially encoded tRNA lysine)

TRNK (HGNC:):

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• PP3: Mitotip and hmtvar scores support pathogenic criterium.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRNK	TRNK.1	n.48G>A		non_coding_transcript_exon_variant	1/1
ATP8	ATP8.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-TK	ENST00000387421.1	n.48G>A		non_coding_transcript_exon_variant	1/1
MT-ATP8	ENST00000361851.1			upstream_gene_variant				P1

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;