rs727503387
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_001134363.3(RBM20):c.1418C>T(p.Ala473Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,550,998 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RBM20 | NM_001134363.3 | c.1418C>T | p.Ala473Val | missense_variant | 4/14 | ENST00000369519.4 | NP_001127835.2 | |
RBM20 | XM_017016103.3 | c.1253C>T | p.Ala418Val | missense_variant | 4/14 | XP_016871592.1 | ||
RBM20 | XM_017016104.3 | c.1034C>T | p.Ala345Val | missense_variant | 4/14 | XP_016871593.1 | ||
RBM20 | XM_047425116.1 | c.1034C>T | p.Ala345Val | missense_variant | 4/14 | XP_047281072.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RBM20 | ENST00000369519.4 | c.1418C>T | p.Ala473Val | missense_variant | 4/14 | 1 | NM_001134363.3 | ENSP00000358532 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152186Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000130 AC: 2AN: 153870Hom.: 0 AF XY: 0.0000123 AC XY: 1AN XY: 81632
GnomAD4 exome AF: 0.00000786 AC: 11AN: 1398812Hom.: 0 Cov.: 31 AF XY: 0.00000870 AC XY: 6AN XY: 689936
GnomAD4 genome AF: 0.0000854 AC: 13AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74346
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 | Sep 30, 2014 | The Ala473Val variant in RBM20 has not been previously reported in individuals w ith cardiomyopathy or in large population studies. Alanine (Ala) at position 473 is not conserved in mammals or evolutionarily distant species and the change to valine (Val) is present in horse, suggesting that this variant may be tolerated . Additional computational prediction tools suggest that the Ala473Val variant m ay not impact the protein, though this information is not predictive enough to r ule out pathogenicity. In summary, the clinical significance of the Ala473Val va riant is uncertain. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 16, 2023 | The p.A473V variant (also known as c.1418C>T), located in coding exon 4 of the RBM20 gene, results from a C to T substitution at nucleotide position 1418. The alanine at codon 473 is replaced by valine, an amino acid with similar properties. This amino acid position is not well 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 | Labcorp Genetics (formerly Invitae), Labcorp | Jul 25, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 05, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at