rs201940876
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 3P and 3B. PM1PP2BP4_ModerateBP6
The NM_000540.3(RYR1):c.3431C>T(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). Synonymous variant affecting the same amino acid position (i.e. P1144P) has been classified as Likely benign.
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.3431C>T | p.Pro1144Leu | missense_variant | 26/106 | ENST00000359596.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.3431C>T | p.Pro1144Leu | missense_variant | 26/106 | 5 | NM_000540.3 | A2 | |
RYR1 | ENST00000355481.8 | c.3431C>T | p.Pro1144Leu | missense_variant | 26/105 | 1 | P4 | ||
RYR1 | ENST00000599547.6 | c.3431C>T | p.Pro1144Leu | missense_variant, NMD_transcript_variant | 26/80 | 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 | Invitae | Jan 01, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at