rs397516598
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BP6BS2
The NM_001134363.3(RBM20):āc.1973C>Gā(p.Ser658Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,551,584 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: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.000017 ( 0 hom. )
Consequence
RBM20
NM_001134363.3 missense
NM_001134363.3 missense
Scores
10
6
Clinical Significance
Conservation
PhyloP100: 7.57
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.3938089).
BP6
?
Variant 10-110812370-C-G is Benign according to our data. Variant chr10-110812370-C-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 43982.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1}.
BS2
?
High AC in GnomAdExome4 at 24 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RBM20 | NM_001134363.3 | c.1973C>G | p.Ser658Cys | missense_variant | 9/14 | ENST00000369519.4 | |
RBM20 | XM_017016103.3 | c.1808C>G | p.Ser603Cys | missense_variant | 9/14 | ||
RBM20 | XM_017016104.3 | c.1589C>G | p.Ser530Cys | missense_variant | 9/14 | ||
RBM20 | XM_047425116.1 | c.1589C>G | p.Ser530Cys | missense_variant | 9/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBM20 | ENST00000369519.4 | c.1973C>G | p.Ser658Cys | missense_variant | 9/14 | 1 | NM_001134363.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152236Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000645 AC: 1AN: 154990Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 82474
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GnomAD4 exome AF: 0.0000172 AC: 24AN: 1399348Hom.: 0 Cov.: 32 AF XY: 0.0000130 AC XY: 9AN XY: 690180
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152236Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74380
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 11, 2013 | The Ser658Cys variant in RBM20 has not been reported in the literature. It has b een identified by our laboratory in 1 Caucasian individual with DCM (LMM unpubli shed data), though it did not segregate with disease in an affected family membe r. The frequency of this variant in large European American and African American populations cannot be determined from the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS/) because coverage at this position was insufficient or unavailable. Serine (Ser) at position 658 is not conserved in mammals, thoug h additional computational analyses (biochemical amino acid properties, AlignGVG D, and SIFT) do not provide strong support for or against an impact to the prote in. Finally, this variant lies within exon 9, which encodes a conserved protein domain where other pathogenic variants have been reported (Brauch 2009, Li 2010) . In summary, additional studies are needed to fully assess the clinical signifi cance of the Ser658Cys variant. - |
Primary familial dilated cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute | - | - - |
Dilated cardiomyopathy 1DD Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 16, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Uncertain
D
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Vest4
MutPred
Loss of phosphorylation at S658 (P = 0.0116);
MVP
ClinPred
D
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at