Variant M-12177-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BS2

The ENST00000387441.1(MT-TH):n.40A>G 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: 3 )

Consequence

MT-TH
ENST00000387441.1 non_coding_transcript_exon

Scores

Mitotip

Uncertain

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

No linked disesase in Mitomap

Conservation

PhyloP100: 0.418

Variant links:

Genes affected

MT-TH (HGNC:7487): (mitochondrially encoded tRNA histidine)

MT-TH links:

TRNH (HGNC:):

TRNH links:

MT-ND4 (HGNC:7459): (mitochondrially encoded NADH dehydrogenase 4) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Part of mitochondrial respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; Parkinson's disease; macular degeneration; and schizophrenia. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2022]

MT-ND4 links:

MT-TS2 (HGNC:7498): (mitochondrially encoded tRNA serine 2 (AGU/C))

MT-TS2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very low frequency in mitomap database: 0.0

BS2

High AC in GnomadMitoHomoplasmic at 5

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNH	TRNH.1 use as main transcript	n.40A>G		non_coding_transcript_exon_variant	1/1
TRNS2	TRNS2.1 use as main transcript			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	Protein	Appris
MT-TH	ENST00000387441.1 linkuse as main transcript	n.40A>G	non_coding_transcript_exon_variant	1/1
MT-ND4	ENST00000361381.2 linkuse as main transcript		downstream_gene_variant		ENSP00000354961	P1
MT-TS2	ENST00000387449.1 linkuse as main transcript		upstream_gene_variant

Frequencies

GnomAD4 exome

Cov.:

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

Mitomap GenBank

AF:

0.0

AC:

Gnomad homoplasmic

AF:

0.000089

AC:

AN:

56434

Gnomad heteroplasmic

AF:

0.0

AC:

AN:

56434

Mitomap

No disease associated.

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Aug 14, 2017

This variant affects the MT-TH gene, which encodes the mitochondrial tRNA for histidine, and has not been reported in the medical literature, is not listed in gene-specific variant databases, nor has it been previously identified in our laboratory. It is also absent from population databases such as MITOMAP. This variant disrupts a moderately conserved nucleotide, and Xenopus tropicalis has a guanine at this position suggesting this variant is evolutionary tolerated. However, based on the available information, the clinical significance of the m.12177A>G variant cannot be determined with certainty. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction