rs950210735
Positions:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_001134363.3(RBM20):c.1201G>A(p.Asp401Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,551,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
RBM20
NM_001134363.3 missense
NM_001134363.3 missense
Scores
8
7
1
Clinical Significance
Conservation
PhyloP100: 9.54
Genes affected
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.817
BS2
?
High AC in GnomAdExome4 at 15 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RBM20 | NM_001134363.3 | c.1201G>A | p.Asp401Asn | missense_variant | 2/14 | ENST00000369519.4 | |
RBM20 | XM_017016103.3 | c.1036G>A | p.Asp346Asn | missense_variant | 2/14 | ||
RBM20 | XM_017016104.3 | c.817G>A | p.Asp273Asn | missense_variant | 2/14 | ||
RBM20 | XM_047425116.1 | c.817G>A | p.Asp273Asn | missense_variant | 2/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBM20 | ENST00000369519.4 | c.1201G>A | p.Asp401Asn | missense_variant | 2/14 | 1 | NM_001134363.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152228Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
3
AN:
152228
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00000648 AC: 1AN: 154254Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 81948
GnomAD3 exomes
AF:
AC:
1
AN:
154254
Hom.:
AF XY:
AC XY:
0
AN XY:
81948
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000107 AC: 15AN: 1399434Hom.: 0 Cov.: 32 AF XY: 0.0000116 AC XY: 8AN XY: 690224
GnomAD4 exome
AF:
AC:
15
AN:
1399434
Hom.:
Cov.:
32
AF XY:
AC XY:
8
AN XY:
690224
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74370
GnomAD4 genome
?
AF:
AC:
3
AN:
152228
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74370
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Dilated cardiomyopathy 1DD Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 04, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RBM20 protein function. ClinVar contains an entry for this variant (Variation ID: 470585). This variant has not been reported in the literature in individuals affected with RBM20-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 401 of the RBM20 protein (p.Asp401Asn). - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 14, 2021 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 08, 2023 | The p.D401N variant (also known as c.1201G>A), located in coding exon 2 of the RBM20 gene, results from a G to A substitution at nucleotide position 1201. The aspartic acid at codon 401 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Vest4
MutPred
Loss of stability (P = 0.1756);
MVP
ClinPred
D
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at