rs542392971
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001134363.3(RBM20):āc.3440G>Cā(p.Ser1147Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000197 in 152,242 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. S1147N) has been classified as Uncertain significance.
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.3440G>C | p.Ser1147Thr | missense_variant | 12/14 | ENST00000369519.4 | |
RBM20 | XM_017016103.3 | c.3275G>C | p.Ser1092Thr | missense_variant | 12/14 | ||
RBM20 | XM_017016104.3 | c.3056G>C | p.Ser1019Thr | missense_variant | 12/14 | ||
RBM20 | XM_047425116.1 | c.3056G>C | p.Ser1019Thr | missense_variant | 12/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBM20 | ENST00000369519.4 | c.3440G>C | p.Ser1147Thr | missense_variant | 12/14 | 1 | NM_001134363.3 | P1 | |
RBM20 | ENST00000471172.1 | n.16G>C | non_coding_transcript_exon_variant | 1/2 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152124Hom.: 0 Cov.: 30
GnomAD4 exome Cov.: 34
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152242Hom.: 0 Cov.: 30 AF XY: 0.0000134 AC XY: 1AN XY: 74452
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1DD Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 21, 2022 | This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 1147 of the RBM20 protein (p.Ser1147Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RBM20-related conditions. ClinVar contains an entry for this variant (Variation ID: 470610). 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. 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. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 24, 2023 | The p.S1147T variant (also known as c.3440G>C), located in coding exon 12 of the RBM20 gene, results from a G to C substitution at nucleotide position 3440. The serine at codon 1147 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at