chr10-110812370-C-G
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
Consequence
NM_001134363.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RBM20 | NM_001134363.3 | c.1973C>G | p.Ser658Cys | missense_variant | Exon 9 of 14 | ENST00000369519.4 | NP_001127835.2 | |
RBM20 | XM_017016103.3 | c.1808C>G | p.Ser603Cys | missense_variant | Exon 9 of 14 | XP_016871592.1 | ||
RBM20 | XM_017016104.3 | c.1589C>G | p.Ser530Cys | missense_variant | Exon 9 of 14 | XP_016871593.1 | ||
RBM20 | XM_047425116.1 | c.1589C>G | p.Ser530Cys | missense_variant | Exon 9 of 14 | XP_047281072.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152236Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000645 AC: 1AN: 154990Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 82474
GnomAD4 exome AF: 0.0000172 AC: 24AN: 1399348Hom.: 0 Cov.: 32 AF XY: 0.0000130 AC XY: 9AN XY: 690180
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152236Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74380
ClinVar
Submissions by phenotype
not specified Uncertain:1
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
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Dilated cardiomyopathy 1DD Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at