rs876657972
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBP6
The NM_001134363.3(RBM20):c.1329C>G(p.Phe443Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000451 in 1,550,774 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000043 ( 0 hom. )
Consequence
RBM20
NM_001134363.3 missense
NM_001134363.3 missense
Scores
1
5
10
Clinical Significance
Conservation
PhyloP100: 1.72
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.21543497).
BP6
?
Variant 10-110783419-C-G is Benign according to our data. Variant chr10-110783419-C-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 229183.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RBM20 | NM_001134363.3 | c.1329C>G | p.Phe443Leu | missense_variant | 3/14 | ENST00000369519.4 | |
RBM20 | XM_017016103.3 | c.1164C>G | p.Phe388Leu | missense_variant | 3/14 | ||
RBM20 | XM_017016104.3 | c.945C>G | p.Phe315Leu | missense_variant | 3/14 | ||
RBM20 | XM_047425116.1 | c.945C>G | p.Phe315Leu | missense_variant | 3/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBM20 | ENST00000369519.4 | c.1329C>G | p.Phe443Leu | missense_variant | 3/14 | 1 | NM_001134363.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152224Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000190 AC: 3AN: 157806Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 83338
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GnomAD4 exome AF: 0.00000429 AC: 6AN: 1398432Hom.: 0 Cov.: 29 AF XY: 0.00000290 AC XY: 2AN XY: 689804
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GnomAD4 genome ? AF: 0.00000656 AC: 1AN: 152342Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74500
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign: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 | Dec 18, 2015 | The p.Phe443Leu variant in RBM20 has not been previously reported in individuals with cardiomyopathy and was absent from large population studies. Computational prediction tools and conservation analysis suggest that the p.Phe443Leu variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of the p.Phe443Le u variant is uncertain. - |
Dilated cardiomyopathy 1DD Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 08, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Vest4
MutPred
Gain of helix (P = 6e-04);
MVP
ClinPred
T
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