rs1060504913
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBP6BP7
The NM_001134363.3(RBM20):c.1962C>T(p.Ser654=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000219 in 1,551,526 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: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
RBM20
NM_001134363.3 synonymous
NM_001134363.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.777
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
?
Variant 10-110812359-C-T is Benign according to our data. Variant chr10-110812359-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 416822.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}. Variant chr10-110812359-C-T is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=0.777 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RBM20 | NM_001134363.3 | c.1962C>T | p.Ser654= | synonymous_variant | 9/14 | ENST00000369519.4 | |
RBM20 | XM_017016103.3 | c.1797C>T | p.Ser599= | synonymous_variant | 9/14 | ||
RBM20 | XM_017016104.3 | c.1578C>T | p.Ser526= | synonymous_variant | 9/14 | ||
RBM20 | XM_047425116.1 | c.1578C>T | p.Ser526= | synonymous_variant | 9/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBM20 | ENST00000369519.4 | c.1962C>T | p.Ser654= | synonymous_variant | 9/14 | 1 | NM_001134363.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152208Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000129 AC: 2AN: 155094Hom.: 0 AF XY: 0.0000121 AC XY: 1AN XY: 82466
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GnomAD4 exome AF: 0.0000229 AC: 32AN: 1399318Hom.: 0 Cov.: 32 AF XY: 0.0000333 AC XY: 23AN XY: 690168
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Dilated cardiomyopathy 1DD Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 11, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 15, 2021 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 25, 2021 | The c.1962C>T variant (also known as p.S654S), located in coding exon 9 of the RBM20 gene, results from a C to T substitution at nucleotide position 1962. This nucleotide substitution does not change the amino acid at codon 654. This variant was detected in a cardiomyopathy/arrhythmia genetic testing cohort; however, clinical details were limited, and additional cardiac variants were detected in some cases (van Lint FHM et al. Neth Heart J, 2019 Jun;27:304-309). This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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