Variant M-4290-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000387365.1(MT-TI):n.28T>C variant causes a non coding transcript exon change. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Mitomap GenBank:

𝑓 0.0 ( AC: 0 )

Consequence

MT-TI
ENST00000387365.1 non_coding_transcript_exon

Scores

Mitotip

Uncertain

Clinical Significance

Uncertain significance criteria provided, single submitter P:1U:1

Progressive-Encephalopathy-/-PEO+myopathy

Conservation

PhyloP100: 3.97

Variant links:

Genes affected

MT-TI (HGNC:7488): (mitochondrially encoded tRNA isoleucine)

MT-TI links:

TRNI (HGNC:):

TRNI links:

MT-ND1 (HGNC:7455): (mitochondrially encoded NADH dehydrogenase 1) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Located in mitochondrial membrane. Part of mitochondrial respiratory chain complex I. Implicated in several diseases, including MELAS syndrome; neurodegenerative disease (multiple); optic nerve disease (multiple); toxic shock syndrome; and type 2 diabetes mellitus. Biomarker of Alzheimer's disease; Parkinson's disease; and multiple sclerosis. [provided by Alliance of Genome Resources, Apr 2022]

MT-ND1 links:

MT-TQ (HGNC:7495): (mitochondrially encoded tRNA glutamine)

MT-TQ links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very low frequency in mitomap database: 0.0

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNI	TRNI.1 use as main transcript	n.28T>C		non_coding_transcript_exon_variant	1/1
TRNQ	TRNQ.1 use as main transcript			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	Protein	Appris
MT-TI	ENST00000387365.1 linkuse as main transcript	n.28T>C	non_coding_transcript_exon_variant	1/1
MT-ND1	ENST00000361390.2 linkuse as main transcript		downstream_gene_variant		ENSP00000354687	P1
MT-TQ	ENST00000387372.1 linkuse as main transcript		downstream_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:

0.0

AC:

AN:

56425

Gnomad heteroplasmic

AF:

0.000018

AC:

AN:

56425

Mitomap

Progressive-Encephalopathy-/-PEO+myopathy

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Encephalopathy, familial progressive necrotizing

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 01, 2004

- -

Juvenile myopathy, encephalopathy, lactic acidosis AND stroke

Uncertain:1

Uncertain significance, 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.4290T>C variant in MT-TI gene is interpreted to be a Unknown Significance variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: PP3, BS4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction