rs1554842673
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP3BP6
The NM_001134363.3(RBM20):c.1969_1970delinsAG(p.Ser657=) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. S657S) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Consequence
RBM20
NM_001134363.3 synonymous
NM_001134363.3 synonymous
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.58
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
BP6
?
Variant 10-110812366-TC-AG is Benign according to our data. Variant chr10-110812366-TC-AG is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 538015.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=3}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RBM20 | NM_001134363.3 | c.1969_1970delinsAG | p.Ser657= | synonymous_variant | 9/14 | ENST00000369519.4 | |
RBM20 | XM_017016103.3 | c.1804_1805delinsAG | p.Ser602= | synonymous_variant | 9/14 | ||
RBM20 | XM_017016104.3 | c.1585_1586delinsAG | p.Ser529= | synonymous_variant | 9/14 | ||
RBM20 | XM_047425116.1 | c.1585_1586delinsAG | p.Ser529= | synonymous_variant | 9/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBM20 | ENST00000369519.4 | c.1969_1970delinsAG | p.Ser657= | synonymous_variant | 9/14 | 1 | NM_001134363.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:3Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 27, 2023 | See Variant Classification Assertion Criteria. - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Dilated cardiomyopathy 1DD Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 25, 2023 | This sequence change affects codon 657 of the RBM20 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the RBM20 protein. This variant is present in population databases (no rsID available, gnomAD 0.0006%). 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: 538015). 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 17, 2021 | - - |
Cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Mar 18, 2016 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 14, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at