18-3067333-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5
The NM_003803.4(MYOM1):c.4987G>A(p.Val1663Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,611,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_003803.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYOM1 | ENST00000356443.9 | c.4987G>A | p.Val1663Met | missense_variant | Exon 38 of 38 | 1 | NM_003803.4 | ENSP00000348821.4 | ||
MYOM1 | ENST00000261606.11 | c.4699G>A | p.Val1567Met | missense_variant | Exon 37 of 37 | 1 | ENSP00000261606.7 | |||
MYOM1 | ENST00000581804.1 | n.477G>A | non_coding_transcript_exon_variant | Exon 3 of 3 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152230Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249186Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 135040
GnomAD4 exome AF: 0.00000754 AC: 11AN: 1459736Hom.: 0 Cov.: 33 AF XY: 0.00000689 AC XY: 5AN XY: 726138
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152230Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74388
ClinVar
Submissions by phenotype
Non-immune hydrops fetalis Pathogenic:1
Likely pathogenic, criteria provided, single submitter | research | Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre | Mar 19, 2013 | - - |
Hypertrophic cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 06, 2024 | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1663 of the MYOM1 protein (p.Val1663Met). This variant is present in population databases (rs751200138, gnomAD 0.006%). This missense change has been observed in individual(s) with non-immune hydrops fetalis (PMID: 26036949, 31130284). ClinVar contains an entry for this variant (Variation ID: 190459). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt MYOM1 protein function with a negative predictive value of 80%. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at