chrX-150596543-C-T
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000252.3(MTM1):c.109C>T(p.Arg37*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000166 in 1,207,780 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. R37R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000252.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MTM1 | NM_000252.3 | c.109C>T | p.Arg37* | stop_gained | Exon 3 of 15 | ENST00000370396.7 | NP_000243.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000893 AC: 1AN: 111959Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34123
GnomAD4 exome AF: 9.13e-7 AC: 1AN: 1095821Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0AN XY: 361569
GnomAD4 genome AF: 0.00000893 AC: 1AN: 111959Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34123
ClinVar
Submissions by phenotype
Severe X-linked myotubular myopathy Pathogenic:2
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This premature translational stop signal has been observed in individual(s) with myotubular myopathy (PMID: 9305655, 28685322). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg37*) in the MTM1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MTM1 are known to be pathogenic (PMID: 9305655, 10063835). ClinVar contains an entry for this variant (Variation ID: 158895). For these reasons, this variant has been classified as Pathogenic. -
not provided Pathogenic:1
The R37X variant in the MTM1 gene has been reported previously in multiple patients with X-linked myotubular myopathy (Laporte et al., 1997; Buj-Bello et al., 1999; Herman et al., 2002). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R37X variant is not observed in large population cohorts (Lek et al., 2016). We interpret R37X as a pathogenic variant. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at