rs183007628
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4BP6BS1BS2
The NM_001134363.3(RBM20):c.1603G>A(p.Val535Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000574 in 1,551,676 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts 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 -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RBM20 | NM_001134363.3 | c.1603G>A | p.Val535Ile | missense_variant | Exon 6 of 14 | ENST00000369519.4 | NP_001127835.2 | |
RBM20 | XM_017016103.3 | c.1438G>A | p.Val480Ile | missense_variant | Exon 6 of 14 | XP_016871592.1 | ||
RBM20 | XM_017016104.3 | c.1219G>A | p.Val407Ile | missense_variant | Exon 6 of 14 | XP_016871593.1 | ||
RBM20 | XM_047425116.1 | c.1219G>A | p.Val407Ile | missense_variant | Exon 6 of 14 | XP_047281072.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000302 AC: 46AN: 152116Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.0000318 AC: 5AN: 157294Hom.: 0 AF XY: 0.0000240 AC XY: 2AN XY: 83176
GnomAD4 exome AF: 0.0000307 AC: 43AN: 1399442Hom.: 0 Cov.: 30 AF XY: 0.0000261 AC XY: 18AN XY: 690232
GnomAD4 genome AF: 0.000302 AC: 46AN: 152234Hom.: 1 Cov.: 32 AF XY: 0.000296 AC XY: 22AN XY: 74426
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1DD Benign:2
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Cardiovascular phenotype Uncertain:1
The p.V535I variant (also known as c.1603G>A), located in coding exon 6 of the RBM20 gene, results from a G to A substitution at nucleotide position 1603. The valine at codon 535 is replaced by isoleucine, an amino acid with highly similar properties. This variant was reported in a patient with dilated cardiomyopathy (DCM) who also carried an alteration in LDB3, and was also detected in association with DCM in an additional cohort; however, details were limited (Li D et al, Clin Transl Sci 2010 Jun; 3(3):90-7; Smith E et al. J Am Heart Assoc. 2022 May;11(9):e024501). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. -
not provided Benign:1
Reported in one individual with DCM; however, this individual also harbored a variant in the LDB3 gene, and there were not a sufficient number of affected family members to assess segregation with disease (Li et al., 2010); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Reported in ClinVar but additional evidence is not available (ClinVar Variant ID# 202044; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 22466703, 20590677, 30547036, 29304022) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at