rs1060503416
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001134363.3(RBM20):āc.3564G>Cā(p.Arg1188Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000715 in 1,398,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1188G) has been classified as Benign.
Frequency
Consequence
NM_001134363.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RBM20 | NM_001134363.3 | c.3564G>C | p.Arg1188Ser | missense_variant | 13/14 | ENST00000369519.4 | |
RBM20 | XM_017016103.3 | c.3399G>C | p.Arg1133Ser | missense_variant | 13/14 | ||
RBM20 | XM_017016104.3 | c.3180G>C | p.Arg1060Ser | missense_variant | 13/14 | ||
RBM20 | XM_047425116.1 | c.3180G>C | p.Arg1060Ser | missense_variant | 13/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBM20 | ENST00000369519.4 | c.3564G>C | p.Arg1188Ser | missense_variant | 13/14 | 1 | NM_001134363.3 | P1 | |
RBM20 | ENST00000471172.1 | n.140G>C | non_coding_transcript_exon_variant | 2/2 | 5 | ||||
RBM20 | ENST00000480343.2 | n.197G>C | non_coding_transcript_exon_variant | 2/3 | 4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 7.15e-7 AC: 1AN: 1398840Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1AN XY: 689838
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1DD Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 09, 2022 | This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 1188 of the RBM20 protein (p.Arg1188Ser). This variant is not present in population databases (gnomAD no frequency). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RBM20 protein function. ClinVar contains an entry for this variant (Variation ID: 411660). This variant has not been reported in the literature in individuals affected with RBM20-related conditions. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 14, 2024 | The p.R1188S variant (also known as c.3564G>C), located in coding exon 13 of the RBM20 gene, results from a G to C substitution at nucleotide position 3564. The arginine at codon 1188 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is well 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 alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at