M-10406-G-A

Position:

• chrM-10406-G-A

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM2 PP3 PP5_Very_Strong

The ENST00000387439.1(MT-TR):​n.2G>A variant causes a non coding transcript exon change. Variant has been reported in ClinVar as Likely pathogenic (★★).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 0)
• Consequence: MT-TR ENST00000387439.1 non_coding_transcript_exon
• Scores: Mitotip Uncertain 16
• Clinical Significance: Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:2 Mitochondrial-myopathy
• Conservation: PhyloP100: 3.98

Genes affected

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

TRNR (HGNC:):

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]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• PP3: Mitotip and hmtvar scores support pathogenic criterium.
• PP5: Variant M-10406-G-A is Pathogenic according to our data. Variant chrM-10406-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 690112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRNR	TRNR.1	n.2G>A		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-TR	ENST00000387439.1	n.2G>A		non_coding_transcript_exon_variant	1/1
MT-ND3	ENST00000361227.2			downstream_gene_variant				P1

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

Mitomap

Mitochondrial-myopathy

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Mitochondrial disease Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

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.10406G>A 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: PM7, PM8, PM9, PM10 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Uncertain	16
Hmtvar	Pathogenic	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1603222826; hg19: chrM-10407;