rs121434469

chrM-4290-T-C

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 13
• Clinical Significance: Uncertain significance criteria provided, single submitter P:1 U:1 Progressive-Encephalopathy-/-PEO+myopathy
• Conservation: PhyloP100: 3.97

Genes affected

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

TRNI (HGNC:):

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

ACMG classification

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	UniProt
TRNI	TRNI.1	n.28T>C		non_coding_transcript_exon_variant	1/1
TRNQ	TRNQ.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-TI	ENST00000387365.1	n.28T>C		non_coding_transcript_exon_variant	1/1
MT-ND1	ENST00000361390.2			downstream_gene_variant				P1
MT-TQ	ENST00000387372.1			downstream_gene_variant

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap GenBank AF: 0.0 AC: 0

Gnomad homoplasmic AF: 0.0 AC: 0 AN: 56425

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56425

Mitomap

Progressive-Encephalopathy-/-PEO+myopathy

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1 Uncertain:1

Revision: criteria provided, single submitter

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
Mitotip	Uncertain	13
Hmtvar	Pathogenic	1.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs121434469; hg19: chrM-4291;