rs1057520187
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_000540.3(RYR1):āc.13548G>Cā(p.Glu4516Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,968 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. E4516G) has been classified as Uncertain significance.
Frequency
Consequence
NM_000540.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.13548G>C | p.Glu4516Asp | missense_variant | 93/106 | ENST00000359596.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.13548G>C | p.Glu4516Asp | missense_variant | 93/106 | 5 | NM_000540.3 | A2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152094Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 249034Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134816
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461874Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8AN XY: 727240
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152094Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74296
ClinVar
Submissions by phenotype
Malignant hyperthermia, susceptibility to, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Dec 01, 2023 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Sep 08, 2016 | - - |
Congenital myopathy with fiber type disproportion;C0751951:Central core myopathy;C1840365:King Denborough syndrome;C1850674:Congenital multicore myopathy with external ophthalmoplegia;C2930980:Malignant hyperthermia, susceptibility to, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Feb 03, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at