chr10-110784856-C-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM1BP4_ModerateBS1_SupportingBS2
The NM_001134363.3(RBM20):c.1494C>A(p.Ser498Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000529 in 1,550,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict 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 -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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RBM20 | NM_001134363.3 | c.1494C>A | p.Ser498Arg | missense_variant | Exon 5 of 14 | ENST00000369519.4 | NP_001127835.2 | |
RBM20 | XM_017016103.3 | c.1329C>A | p.Ser443Arg | missense_variant | Exon 5 of 14 | XP_016871592.1 | ||
RBM20 | XM_017016104.3 | c.1110C>A | p.Ser370Arg | missense_variant | Exon 5 of 14 | XP_016871593.1 | ||
RBM20 | XM_047425116.1 | c.1110C>A | p.Ser370Arg | missense_variant | Exon 5 of 14 | XP_047281072.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000130 AC: 2AN: 153882Hom.: 0 AF XY: 0.0000245 AC XY: 2AN XY: 81618
GnomAD4 exome AF: 0.0000579 AC: 81AN: 1397880Hom.: 0 Cov.: 30 AF XY: 0.0000522 AC XY: 36AN XY: 689522
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74352
ClinVar
Submissions by phenotype
not provided Uncertain:2
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Dilated cardiomyopathy 1DD Uncertain:1Benign:1
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not specified Uncertain:1
The p.Ser498Arg variant in RBM20 has not been previously reported in individuals with cardiomyopathy or in large population studies. Computational prediction to ols and conservation analysis do not provide strong support for or against an im pact to the protein. In summary, the clinical significance of the p.Ser498Arg va riant is uncertain. -
Cardiomyopathy Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at