rs931169553
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_000540.3(RYR1):āc.13448T>Gā(p.Val4483Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000623 in 1,604,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V4483M) has been classified as Uncertain significance.
Frequency
Consequence
NM_000540.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR1 | NM_000540.3 | c.13448T>G | p.Val4483Gly | missense_variant | 92/106 | ENST00000359596.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.13448T>G | p.Val4483Gly | missense_variant | 92/106 | 5 | NM_000540.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000264 AC: 4AN: 151262Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000859 AC: 2AN: 232850Hom.: 0 AF XY: 0.0000159 AC XY: 2AN XY: 126062
GnomAD4 exome AF: 0.00000413 AC: 6AN: 1452766Hom.: 0 Cov.: 32 AF XY: 0.00000416 AC XY: 3AN XY: 721698
GnomAD4 genome ? AF: 0.0000264 AC: 4AN: 151262Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 73810
ClinVar
Submissions by phenotype
RYR1-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 30, 2023 | This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 4483 of the RYR1 protein (p.Val4483Gly). 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) performed at Invitae indicates that this missense variant is not expected to disrupt RYR1 protein function. ClinVar contains an entry for this variant (Variation ID: 569228). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Oct 02, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at