M-8296-A-G

Position:

• chrM-8296-A-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP3 BP6_Moderate BS2

The ENST00000387421.1(MT-TK):​n.2A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.00060 (AC: 38)
• Consequence: MT-TK ENST00000387421.1 non_coding_transcript_exon
• Scores: Mitotip Uncertain 16
• Clinical Significance: Benign criteria provided, single submitter P:1 B:1 O:1 DMDF-/-MERRF-/-HCM-/-epilepsy-/-hearing-loss
• Conservation: PhyloP100: 1.81

Genes affected

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

TRNK (HGNC:):

MT-CO2 (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 Likely_benign. Variant got -5 ACMG points.

• PP3: Mitotip and hmtvar scores support pathogenic criterium.
• BP6: Variant M-8296-A-G is Benign according to our data. Variant chrM-8296-A-G is described in ClinVar as [Benign]. Clinvar id is 9584.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 25

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNK	TRNK.1	n.2A>G		non_coding_transcript_exon_variant	1/1
COX2	COX2.1			downstream_gene_variant			YP_003024029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-TK	ENST00000387421.1	n.2A>G		non_coding_transcript_exon_variant	1/1
MT-CO2	ENST00000361739.1			downstream_gene_variant				ENSP00000354876	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: 0.00060 AC: 38

Gnomad homoplasmic AF: 0.00044 AC: 25 AN: 56432

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56432

Alfa AF: 0.000212 Hom.: 1

Mitomap

DMDF-/-MERRF-/-HCM-/-epilepsy-/-hearing-loss

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1 Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

Juvenile myopathy, encephalopathy, lactic acidosis AND stroke Benign:1 Other:1

Benign, criteria provided, single submitter	clinical testing	Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine	Jul 12, 2019	The NC_012920.1:m.8296A>G variant in MT-TK gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: BS1, BS2 -
not provided, no classification provided	literature only	GeneReviews	-	- -

Diabetes-deafness syndrome maternally transmitted Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 17, 1998

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	16
Hmtvar	Pathogenic	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs118192102; hg19: chrM-8297;