rs202225176
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBP6
The NM_000540.3(RYR1):c.5287C>T(p.Pro1763Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,613,714 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1763L) 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 -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR1 | NM_000540.3 | c.5287C>T | p.Pro1763Ser | missense_variant | 34/106 | ENST00000359596.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.5287C>T | p.Pro1763Ser | missense_variant | 34/106 | 5 | NM_000540.3 | A2 | |
RYR1 | ENST00000355481.8 | c.5287C>T | p.Pro1763Ser | missense_variant | 34/105 | 1 | P4 | ||
RYR1 | ENST00000599547.6 | c.5287C>T | p.Pro1763Ser | missense_variant, NMD_transcript_variant | 34/80 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152198Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000530 AC: 13AN: 245134Hom.: 0 AF XY: 0.0000301 AC XY: 4AN XY: 132946
GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461398Hom.: 0 Cov.: 33 AF XY: 0.0000165 AC XY: 12AN XY: 726984
GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152316Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74460
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Aug 20, 2019 | - - |
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 | Aug 23, 2021 | - - |
RYR1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at