rs118192104

chrM-8361-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3 PP5

The ENST00000387421.1(MT-TK):n.67G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Mitomap GenBank: Absent
• Consequence: MT-TK ENST00000387421.1 non_coding_transcript_exon
• Scores: Mitotip Uncertain 15
• Clinical Significance: Pathogenic no assertion criteria provided P:1 O:1 MERRF
• Conservation: PhyloP100: 0.0280

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 4 ACMG points.

• PM2: No frequency data in Mitomap. Probably very rare.
• PP3: Mitotip and hmtvar scores support pathogenic criterium.
• PP5: Variant M-8361-G-A is Pathogenic according to our data. Variant chrM-8361-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 9585.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRNK	TRNK.1	n.67G>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.67G>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

MERRF

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

MERRF syndrome Pathogenic:1 Other:1

Pathogenic, no assertion criteria provided	literature only	OMIM	Dec 01, 2003	- -
not provided, no classification provided	literature only	GeneReviews	-	Pathogenic variants identified in approximately 10% of persons w/MERRF -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	15
Hmtvar	Pathogenic	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs118192104; hg19: chrM-8362;