rs374117753
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_001036.6(RYR3):c.14127C>T(p.Cys4709Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,614,054 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000084 ( 1 hom. )
Consequence
RYR3
NM_001036.6 synonymous
NM_001036.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.838
Genes affected
RYR3 (HGNC:10485): (ryanodine receptor 3) The protein encoded by this gene is a ryanodine receptor, which functions to release calcium from intracellular storage for use in many cellular processes. For example, the encoded protein is involved in skeletal muscle contraction by releasing calcium from the sarcoplasmic reticulum followed by depolarization of T-tubules. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.3).
BP6
Variant 15-33857899-C-T is Benign according to our data. Variant chr15-33857899-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 461875.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.838 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RYR3 | NM_001036.6 | c.14127C>T | p.Cys4709Cys | synonymous_variant | 99/104 | ENST00000634891.2 | NP_001027.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RYR3 | ENST00000634891.2 | c.14127C>T | p.Cys4709Cys | synonymous_variant | 99/104 | 1 | NM_001036.6 | ENSP00000489262.1 |
Frequencies
GnomAD3 genomes AF: 0.000276 AC: 42AN: 152138Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000104 AC: 26AN: 249136Hom.: 0 AF XY: 0.0000888 AC XY: 12AN XY: 135160
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GnomAD4 exome AF: 0.0000841 AC: 123AN: 1461798Hom.: 1 Cov.: 30 AF XY: 0.0000866 AC XY: 63AN XY: 727214
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GnomAD4 genome AF: 0.000296 AC: 45AN: 152256Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74446
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Epileptic encephalopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 23, 2023 | - - |
RYR3-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 20, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
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Benign
DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at