rs193922835
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_000540.3(RYR1):c.10086C>G(p.Ile3362Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. I3362I) 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR1 | NM_000540.3 | c.10086C>G | p.Ile3362Met | missense_variant | 67/106 | ENST00000359596.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.10086C>G | p.Ile3362Met | missense_variant | 67/106 | 5 | NM_000540.3 | A2 | |
RYR1 | ENST00000355481.8 | c.10086C>G | p.Ile3362Met | missense_variant | 67/105 | 1 | P4 | ||
RYR1 | ENST00000594335.5 | c.*829C>G | 3_prime_UTR_variant, NMD_transcript_variant | 27/49 | 1 | ||||
RYR1 | ENST00000599547.6 | c.*845C>G | 3_prime_UTR_variant, NMD_transcript_variant | 66/80 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461812Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727226
GnomAD4 genome ? Cov.: 31
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 | Mar 07, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at