rs201940876
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 3P and 3B. PM1PP2BP4_ModerateBP6
The NM_000540.3(RYR1):βc.3431C>Tβ(p.Pro1144Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000632 in 1,614,192 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Conflicting classifications of pathogenicity (no stars).
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RYR1 | NM_000540.3 | c.3431C>T | p.Pro1144Leu | missense_variant | 26/106 | ENST00000359596.8 | NP_000531.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.3431C>T | p.Pro1144Leu | missense_variant | 26/106 | 5 | NM_000540.3 | ENSP00000352608.2 | ||
RYR1 | ENST00000355481.8 | c.3431C>T | p.Pro1144Leu | missense_variant | 26/105 | 1 | ENSP00000347667.3 | |||
RYR1 | ENST00000599547.6 | n.3431C>T | non_coding_transcript_exon_variant | 26/80 | 2 | ENSP00000471601.2 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152196Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000139 AC: 35AN: 251464Hom.: 0 AF XY: 0.000206 AC XY: 28AN XY: 135912
GnomAD4 exome AF: 0.0000670 AC: 98AN: 1461878Hom.: 1 Cov.: 31 AF XY: 0.0000894 AC XY: 65AN XY: 727244
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152314Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74476
ClinVar
Submissions by phenotype
Malignant hyperthermia, susceptibility to, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jul 01, 2013 | - - |
RYR1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 01, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at