Variant M-12161-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4BP6_ModerateBS2

The ENST00000387441.1(MT-TH):n.24T>C 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 0.00090 ( AC: 57 )

Consequence

MT-TH
ENST00000387441.1 non_coding_transcript_exon

Scores

Mitotip

Uncertain

9.4

Clinical Significance

Benign criteria provided, single submitter B:1

No linked disesase in Mitomap

Conservation

PhyloP100: 0.179

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Mitotip and hmtvar scores support benign criterium.

BP6

Variant M-12161-T-C is Benign according to our data. Variant chrM-12161-T-C is described in ClinVar as [Benign]. Clinvar id is 690137.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomadMitoHomoplasmic at 19

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNH	TRNH.1 use as main transcript	n.24T>C		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.24T>C	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:

0.00090

AC:

Gnomad homoplasmic

AF:

0.00034

AC:

AN:

56434

Gnomad heteroplasmic

AF:

0.000018

AC:

AN:

56434

Alfa

AF:

0.000890

Hom.:

Mitomap

No disease associated.

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Juvenile myopathy, encephalopathy, lactic acidosis AND stroke

Benign: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.12161T>C variant in MT-TH 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, BS4, BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction