rs876657916
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003803.4(MYOM1):c.1668delG(p.Trp556CysfsTer9) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,696 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_003803.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYOM1 | ENST00000356443.9 | c.1668delG | p.Trp556CysfsTer9 | frameshift_variant | Exon 12 of 38 | 1 | NM_003803.4 | ENSP00000348821.4 | ||
MYOM1 | ENST00000261606.11 | c.1668delG | p.Trp556CysfsTer9 | frameshift_variant | Exon 12 of 37 | 1 | ENSP00000261606.7 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248458Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134810
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460696Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726666
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
The p.Trp556fs variant in MYOM1 has not been previously reported in individuals with cardiomyopathy and was absent from large population studies, though the abi lity of these studies to accurately detect indels may be limited. This variant i s predicted to cause a frameshift, which alters the protein's amino acid sequenc e beginning at position 556 and leads to a premature termination codon 9 amino a cids downstream. This alteration is then predicted to lead to a truncated or abs ent protein. Despite the predicted severe impact on the protein, the variant spe ctrum and mode of inheritance for the MYOM1 gene is not well understood. As a re sult, the clinical significance of the p.Trp556fs variant is uncertain. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at