rs727505308
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001134363.3(RBM20):āc.1259A>Gā(p.Lys420Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000286 in 1,399,412 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000029 ( 0 hom. )
Consequence
RBM20
NM_001134363.3 missense
NM_001134363.3 missense
Scores
2
5
9
Clinical Significance
Conservation
PhyloP100: 7.09
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.2385329).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RBM20 | NM_001134363.3 | c.1259A>G | p.Lys420Arg | missense_variant | 2/14 | ENST00000369519.4 | |
RBM20 | XM_017016103.3 | c.1094A>G | p.Lys365Arg | missense_variant | 2/14 | ||
RBM20 | XM_017016104.3 | c.875A>G | p.Lys292Arg | missense_variant | 2/14 | ||
RBM20 | XM_047425116.1 | c.875A>G | p.Lys292Arg | missense_variant | 2/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBM20 | ENST00000369519.4 | c.1259A>G | p.Lys420Arg | missense_variant | 2/14 | 1 | NM_001134363.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000649 AC: 1AN: 154122Hom.: 0 AF XY: 0.0000122 AC XY: 1AN XY: 81888
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GnomAD4 exome AF: 0.00000286 AC: 4AN: 1399412Hom.: 0 Cov.: 32 AF XY: 0.00000435 AC XY: 3AN XY: 690212
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GnomAD4 genome ? Cov.: 32
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Cov.:
32
Bravo
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:3Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Dilated cardiomyopathy 1DD Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 10, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 25, 2023 | - - |
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 Lys420Arg variant in RBM20 gene has not been previously reported in individu als with cardiomyopathy or in large population studies. Computational prediction tools and conservation analysis suggest that the Lys420Arg variant may not impa ct the protein, though this information is not predictive enough to rule out pat hogenicity. In summary, the clinical significance of the Lys420Arg variant is un certain. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 26, 2020 | The p.K420R variant (also known as c.1259A>G), located in coding exon 2 of the RBM20 gene, results from an A to G substitution at nucleotide position 1259. The lysine at codon 420 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is highly 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. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Vest4
MutPred
Loss of loop (P = 0.0203);
MVP
ClinPred
D
GERP RS
gMVP
Splicing
Name
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at