rs781353247
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_006790.3(MYOT):c.372delA(p.Ala125LeufsTer5) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,946 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_006790.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYOT | NM_006790.3 | c.372delA | p.Ala125LeufsTer5 | frameshift_variant | Exon 3 of 10 | ENST00000239926.9 | NP_006781.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYOT | ENST00000239926.9 | c.372delA | p.Ala125LeufsTer5 | frameshift_variant | Exon 3 of 10 | 1 | NM_006790.3 | ENSP00000239926.4 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152142Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251408Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135882
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461804Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 727204
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74336
ClinVar
Submissions by phenotype
not provided Uncertain:2
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Reported previously in two patients from a cohort of patients with unexplained limb-girdle muscle weakness; however, no specific clinical information was provided (PMID: 32528171); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is not a known mechanism of disease; This variant is associated with the following publications: (PMID: 32528171) -
Myofibrillar myopathy 3 Uncertain:2
This premature translational stop signal has been observed in individual(s) with clinical features of MYOT-related conditions (PMID: 32528171). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 464370). This variant is present in population databases (rs781353247, gnomAD 0.002%). This sequence change creates a premature translational stop signal (p.Ala125Leufs*5) in the MYOT gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in MYOT cause disease. -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at