rs200625526
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_000540.3(RYR1):c.4979G>A(p.Arg1660His) variant causes a missense change. The variant allele was found at a frequency of 0.00000373 in 1,608,484 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. R1660G) 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.4979G>A | p.Arg1660His | missense_variant | 34/106 | ENST00000359596.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.4979G>A | p.Arg1660His | missense_variant | 34/106 | 5 | NM_000540.3 | A2 | |
RYR1 | ENST00000355481.8 | c.4979G>A | p.Arg1660His | missense_variant | 34/105 | 1 | P4 | ||
RYR1 | ENST00000599547.6 | c.4979G>A | p.Arg1660His | missense_variant, NMD_transcript_variant | 34/80 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152190Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000124 AC: 3AN: 241478Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 132218
GnomAD4 exome AF: 0.00000343 AC: 5AN: 1456294Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 724678
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74342
ClinVar
Submissions by phenotype
RYR1-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 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) 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: 544445). This missense change has been observed in individual(s) with clinical features of RYR1-related conditions (Invitae). This variant is present in population databases (rs200625526, gnomAD 0.009%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1660 of the RYR1 protein (p.Arg1660His). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 04, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at