rs1060503417
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_001134363.3(RBM20):āc.299T>Gā(p.Leu100Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000114 in 1,399,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. L100F) has been classified as Uncertain significance.
Frequency
Consequence
NM_001134363.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RBM20 | NM_001134363.3 | c.299T>G | p.Leu100Arg | missense_variant | 2/14 | ENST00000369519.4 | |
RBM20 | XM_017016103.3 | c.134T>G | p.Leu45Arg | missense_variant | 2/14 | ||
RBM20 | XM_017016104.3 | c.-86T>G | 5_prime_UTR_variant | 2/14 | |||
RBM20 | XM_047425116.1 | c.-86T>G | 5_prime_UTR_variant | 2/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBM20 | ENST00000369519.4 | c.299T>G | p.Leu100Arg | missense_variant | 2/14 | 1 | NM_001134363.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000128 AC: 2AN: 156570Hom.: 0 AF XY: 0.0000121 AC XY: 1AN XY: 82946
GnomAD4 exome AF: 0.0000114 AC: 16AN: 1399446Hom.: 0 Cov.: 32 AF XY: 0.0000130 AC XY: 9AN XY: 690220
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1DD Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 14, 2021 | This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a RBM20-related disease. This sequence change replaces leucine with arginine at codon 100 of the RBM20 protein (p.Leu100Arg). The leucine residue is weakly conserved and there is a moderate physicochemical difference between leucine and arginine. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Not Scored"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 10, 2024 | The p.L100R variant (also known as c.299T>G), located in coding exon 2 of the RBM20 gene, results from a T to G substitution at nucleotide position 299. The leucine at codon 100 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at