18-3102501-C-T
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_003803.4(MYOM1):c.3548G>A(p.Arg1183Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000227 in 1,612,752 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. R1183R) has been classified as Likely benign.
Frequency
Consequence
NM_003803.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYOM1 | NM_003803.4 | c.3548G>A | p.Arg1183Gln | missense_variant | 23/38 | ENST00000356443.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYOM1 | ENST00000356443.9 | c.3548G>A | p.Arg1183Gln | missense_variant | 23/38 | 1 | NM_003803.4 | P2 | |
MYOM1 | ENST00000261606.11 | c.3260G>A | p.Arg1087Gln | missense_variant | 22/37 | 1 | A2 |
Frequencies
GnomAD3 genomes AF: 0.000237 AC: 36AN: 152094Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000274 AC: 68AN: 248046Hom.: 0 AF XY: 0.000327 AC XY: 44AN XY: 134568
GnomAD4 exome AF: 0.000226 AC: 330AN: 1460540Hom.: 6 Cov.: 30 AF XY: 0.000215 AC XY: 156AN XY: 726510
GnomAD4 genome AF: 0.000237 AC: 36AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.000323 AC XY: 24AN XY: 74418
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 30, 2015 | The p.Arg1183Gln variant in MYOM1 has not been previously reported in individual s with cardiomyopathy, but has been identified in 27/66568 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs147050513). Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predict ive enough to determine pathogenicity. In summary, the clinical significance of the p.Arg1183Gln variant is uncertain. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Mar 30, 2021 | MYOM1 NM_003803.3 exon 23 p.Arg1183Gln (c.3548G>A): This variant has not been reported in the literature and is present in 0.3% (34/10118) of Ashkenazi Jewish alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/18-3102499-C-T). This variant is present in ClinVar (Variation ID:229025). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
MYOM1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 25, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Hypertrophic cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 08, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at