rs200144997
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 3P and 3B. PM1PP2BP4_ModerateBP6
The NM_000540.3(RYR1):c.10564C>A(p.Leu3522Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000595 in 1,613,490 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). Synonymous variant affecting the same amino acid position (i.e. L3522L) 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.10564C>A | p.Leu3522Met | missense_variant | 71/106 | ENST00000359596.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.10564C>A | p.Leu3522Met | missense_variant | 71/106 | 5 | NM_000540.3 | A2 | |
RYR1 | ENST00000355481.8 | c.10549C>A | p.Leu3517Met | missense_variant | 70/105 | 1 | P4 | ||
RYR1 | ENST00000594335.5 | c.*1292C>A | 3_prime_UTR_variant, NMD_transcript_variant | 30/49 | 1 | ||||
RYR1 | ENST00000599547.6 | c.*1323C>A | 3_prime_UTR_variant, NMD_transcript_variant | 70/80 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151634Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.000330 AC: 83AN: 251330Hom.: 0 AF XY: 0.000206 AC XY: 28AN XY: 135894
GnomAD4 exome AF: 0.0000643 AC: 94AN: 1461856Hom.: 0 Cov.: 32 AF XY: 0.0000440 AC XY: 32AN XY: 727232
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151634Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 74006
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 14, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 05, 2013 | - - |
Malignant hyperthermia, susceptibility to, 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Nov 06, 2022 | - - |
RYR1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at