M-4372-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP5_Strong
Variant has been reported in ClinVar as Uncertain significance (★★★).
Frequency
Consequence
missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TRNQ | unassigned_transcript_4791 | c.29G>A | p.Arg10Lys | missense_variant | Exon 1 of 1 | |||
ND2 | unassigned_transcript_4793 | c.-98C>T | upstream_gene_variant | |||||
TRNM | unassigned_transcript_4792 | c.-30C>T | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|
Frequencies
GnomAD4 exome Cov.: 0
Mitomap
ClinVar
Submissions by phenotype
MELAS syndrome Pathogenic:1
The NC_012920.1:m.4372C>T variant in MT-TQ gene is interpreted to be a Likely Pathogenic variant based on the modified ACMG guidelines (unpublished).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: PM2 PM9, PP3, PP6 -
Mitochondrial disease Uncertain:1
The m.4372C>T variant in MT-TQ has been reported in one individual with primary mitochondrial disease to date however clinical details are not provided (PMIDs: 23463613, 31965079). The variant was present in blood of the proband at 22.8% heteroplasmy and was reportedly absent in an unspecified tissue from the mother (PM6_supporting; PMIDs: 23463613, 31965079). There are no other families reported in the medical literature to our knowledge. This variant is absent in the GenBank dataset, Helix dataset, and gnomAD v3.1.2 (PM2_supporting). Computational predictors are conflicting (MitoTIP: 71.3%; HmtVAR: 0.25). There are no cybrids, single fiber studies, or other functional assays reported on this variant. In summary, this variant meets criteria to be classified as uncertain significance for primary mitochondrial disease inherited in a mitochondrial manner. This classification was approved by the NICHD/NINDS U24 ClinGen Mitochondrial Disease Variant Curation Expert Panel on September 24, 2024. Mitochondrial DNA-specific ACMG/AMP criteria applied (PMID: 32906214): PM6_supporting, PM2_supporting. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at