chr10-110780972-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001134363.3(RBM20):āc.363C>Gā(p.Asn121Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,399,448 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 (ā ). Synonymous variant affecting the same amino acid position (i.e. N121N) has been classified as Likely benign.
Frequency
Consequence
NM_001134363.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RBM20 | NM_001134363.3 | c.363C>G | p.Asn121Lys | missense_variant | 2/14 | ENST00000369519.4 | NP_001127835.2 | |
RBM20 | XM_017016103.3 | c.198C>G | p.Asn66Lys | missense_variant | 2/14 | XP_016871592.1 | ||
RBM20 | XM_017016104.3 | c.-22C>G | 5_prime_UTR_variant | 2/14 | XP_016871593.1 | |||
RBM20 | XM_047425116.1 | c.-22C>G | 5_prime_UTR_variant | 2/14 | XP_047281072.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RBM20 | ENST00000369519.4 | c.363C>G | p.Asn121Lys | missense_variant | 2/14 | 1 | NM_001134363.3 | ENSP00000358532 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000143 AC: 2AN: 1399448Hom.: 0 Cov.: 32 AF XY: 0.00000290 AC XY: 2AN XY: 690226
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1DD Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 26, 2023 | 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. This variant has not been reported in the literature in individuals affected with RBM20-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 121 of the RBM20 protein (p.Asn121Lys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at