rs148540135
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PP2PP3_Moderate
The NM_000540.3(RYR1):c.14468C>T(p.Thr4823Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,614,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. T4823T) 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 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR1 | NM_000540.3 | c.14468C>T | p.Thr4823Met | missense_variant | 100/106 | ENST00000359596.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.14468C>T | p.Thr4823Met | missense_variant | 100/106 | 5 | NM_000540.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152158Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251410Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135882
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461884Hom.: 0 Cov.: 33 AF XY: 0.0000124 AC XY: 9AN XY: 727246
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152158Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4AN XY: 74338
ClinVar
Submissions by phenotype
Malignant hyperthermia, susceptibility to, 1 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Jun 15, 2023 | - - |
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 20, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 30, 2022 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Identified via exome sequencing in a cohort of individuals, although clinical information was not provided (Amendola LM et al., 2015); This variant is associated with the following publications: (PMID: 34426522, 20681998, 25637381) - |
Congenital multicore myopathy with external ophthalmoplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Central core myopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Congenital myopathy Uncertain:1
Uncertain significance, no assertion criteria provided | research | CSER _CC_NCGL, University of Washington | Jun 01, 2014 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at