rs919432113
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001134363.3(RBM20):c.1160C>T(p.Ala387Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000503 in 1,551,710 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A387T) 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 -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RBM20 | NM_001134363.3 | c.1160C>T | p.Ala387Val | missense_variant | 2/14 | ENST00000369519.4 | |
RBM20 | XM_017016103.3 | c.995C>T | p.Ala332Val | missense_variant | 2/14 | ||
RBM20 | XM_017016104.3 | c.776C>T | p.Ala259Val | missense_variant | 2/14 | ||
RBM20 | XM_047425116.1 | c.776C>T | p.Ala259Val | missense_variant | 2/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBM20 | ENST00000369519.4 | c.1160C>T | p.Ala387Val | missense_variant | 2/14 | 1 | NM_001134363.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152212Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000646 AC: 1AN: 154780Hom.: 0 AF XY: 0.0000122 AC XY: 1AN XY: 82128
GnomAD4 exome AF: 0.0000543 AC: 76AN: 1399498Hom.: 0 Cov.: 32 AF XY: 0.0000565 AC XY: 39AN XY: 690262
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74366
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1DD Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2023 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 387 of the RBM20 protein (p.Ala387Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with RBM20-related conditions. ClinVar contains an entry for this variant (Variation ID: 411649). 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) performed at Invitae indicates that this missense variant is not expected to disrupt RBM20 protein function. 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. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 28, 2023 | The c.1160C>T (p.A387V) alteration is located in exon 2 (coding exon 2) of the RBM20 gene. This alteration results from a C to T substitution at nucleotide position 1160, causing the alanine (A) at amino acid position 387 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at