Variant M-10408-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate

The ENST00000387439.1(MT-TR):n.4T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Mitomap GenBank:

Absent

Consequence

MT-TR
ENST00000387439.1 non_coding_transcript_exon

Scores

Mitotip

Uncertain

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Unspecified-patient-from-clinical-lab

Conservation

PhyloP100: -0.0140

Variant links:

Genes affected

MT-TR (HGNC:7496): (mitochondrially encoded tRNA arginine)

MT-TR links:

TRNR (HGNC:):

TRNR links:

MT-ND3 (HGNC:7458): (mitochondrially encoded NADH dehydrogenase 3) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone. Part of mitochondrial respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; Leigh disease; and Parkinson's disease. [provided by Alliance of Genome Resources, Apr 2022]

MT-ND3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

No frequency data in Mitomap. Probably very rare.

PP5

Variant M-10408-T-C is Pathogenic according to our data. Variant chrM-10408-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 690113.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNR	TRNR.1 use as main transcript	n.4T>C		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-TR	ENST00000387439.1 linkuse as main transcript	n.4T>C		non_coding_transcript_exon_variant	1/1
MT-ND3	ENST00000361227.2 linkuse as main transcript			downstream_gene_variant				ENSP00000355206	P1

Frequencies

GnomAD4 exome

Cov.:

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

Mitomap

Unspecified-patient-from-clinical-lab

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Juvenile myopathy, encephalopathy, lactic acidosis AND stroke

Pathogenic:1

Likely pathogenic, 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.10408T>C variant in MT-TR gene is interpreted to be a Likely Pathogenic variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: PM8, PM10, PP3, PP6, PP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction