chrM-10406-G-A

Position:

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM2PP3PP5_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
Variant links:
Genes affected
MT-TR (HGNC:7496): (mitochondrially encoded tRNA arginine)
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]

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ACMG classification

Classification made for transcript

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 Protein UniProt
TRNRTRNR.1 use as main transcriptn.2G>A non_coding_transcript_exon_variant 1/1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MT-TRENST00000387439.1 linkuse as main transcriptn.2G>A non_coding_transcript_exon_variant 1/1
MT-ND3ENST00000361227.2 linkuse as main transcript downstream_gene_variant ENSP00000355206 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
LINK: link

Submissions by phenotype

Mitochondrial disease Pathogenic:1
Pathogenic, criteria provided, single submitterclinical testingMendelicsMay 04, 2022- -
Juvenile myopathy, encephalopathy, lactic acidosis AND stroke Pathogenic:1
Likely pathogenic, criteria provided, single submitterclinical testingWong Mito Lab, Molecular and Human Genetics, Baylor College of MedicineJul 12, 2019The 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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1603222826; hg19: chrM-10407; API