chr19-38494499-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_000540.3(RYR1):c.6422C>T(p.Ala2141Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000868 in 1,613,480 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2141S) has been classified as Uncertain significance.
Frequency
Consequence
NM_000540.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR1 | NM_000540.3 | c.6422C>T | p.Ala2141Val | missense_variant | 39/106 | ENST00000359596.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.6422C>T | p.Ala2141Val | missense_variant | 39/106 | 5 | NM_000540.3 | A2 | |
RYR1 | ENST00000355481.8 | c.6422C>T | p.Ala2141Val | missense_variant | 39/105 | 1 | P4 | ||
RYR1 | ENST00000599547.6 | c.6422C>T | p.Ala2141Val | missense_variant, NMD_transcript_variant | 39/80 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152206Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250510Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135612
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461156Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 726874
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152324Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1AN XY: 74474
ClinVar
Submissions by phenotype
RYR1-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 29, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2141 of the RYR1 protein (p.Ala2141Val). This variant is present in population databases (rs201293931, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 544406). 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. 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Oct 29, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at