chr10-110812735-G-A
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_001134363.3(RBM20):c.2338G>A(p.Gly780Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000206 in 1,551,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G780W) has been classified as Uncertain significance.
Frequency
Consequence
NM_001134363.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RBM20 | NM_001134363.3 | c.2338G>A | p.Gly780Arg | missense_variant | 9/14 | ENST00000369519.4 | |
RBM20 | XM_017016103.3 | c.2173G>A | p.Gly725Arg | missense_variant | 9/14 | ||
RBM20 | XM_017016104.3 | c.1954G>A | p.Gly652Arg | missense_variant | 9/14 | ||
RBM20 | XM_047425116.1 | c.1954G>A | p.Gly652Arg | missense_variant | 9/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBM20 | ENST00000369519.4 | c.2338G>A | p.Gly780Arg | missense_variant | 9/14 | 1 | NM_001134363.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152190Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000383 AC: 6AN: 156488Hom.: 0 AF XY: 0.0000603 AC XY: 5AN XY: 82940
GnomAD4 exome AF: 0.0000214 AC: 30AN: 1399430Hom.: 0 Cov.: 32 AF XY: 0.0000304 AC XY: 21AN XY: 690222
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74352
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 03, 2015 | The p.Gly780Arg variant in RBM20 has not been previously reported in individuals with cardiomyopathy, but has been identified in 2/7908 South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). Comp utational prediction tools and conservation analysis do not provide strong suppo rt for or against an impact to the protein. In summary, the clinical significanc e of the p.Gly780Arg variant is uncertain. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 07, 2020 | Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 229193; Landrum et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function - |
Dilated cardiomyopathy 1DD Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 04, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at