rs397516595
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_001134363.3(RBM20):c.1459G>A(p.Val487Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000187 in 1,550,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001134363.3 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 |
---|---|---|---|---|---|---|---|
RBM20 | NM_001134363.3 | c.1459G>A | p.Val487Met | missense_variant | 5/14 | ENST00000369519.4 | |
RBM20 | XM_017016103.3 | c.1294G>A | p.Val432Met | missense_variant | 5/14 | ||
RBM20 | XM_017016104.3 | c.1075G>A | p.Val359Met | missense_variant | 5/14 | ||
RBM20 | XM_047425116.1 | c.1075G>A | p.Val359Met | missense_variant | 5/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBM20 | ENST00000369519.4 | c.1459G>A | p.Val487Met | missense_variant | 5/14 | 1 | NM_001134363.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152128Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000130 AC: 2AN: 154050Hom.: 0 AF XY: 0.0000122 AC XY: 1AN XY: 81738
GnomAD4 exome AF: 0.0000186 AC: 26AN: 1398600Hom.: 0 Cov.: 30 AF XY: 0.0000188 AC XY: 13AN XY: 689884
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152128Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74316
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 | Jun 01, 2018 | proposed classification - variant undergoing re-assessment, contact laboratory - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 26, 2023 | The p.V487M variant (also known as c.1459G>A), located in coding exon 5 of the RBM20 gene, results from a G to A substitution at nucleotide position 1459. The valine at codon 487 is replaced by methionine, an amino acid with highly similar properties. This variant has been detected in a pediatric dilated cardiomyopathy case; however details were limited (Pugh TJ et al. Genet Med, 2014 Aug;16:601-8). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Dilated cardiomyopathy 1DD Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at