rs374117753
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_001036.6(RYR3):c.14127C>T(p.Cys4709=) 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 Benign. Variant got -9 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_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.838 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR3 | NM_001036.6 | c.14127C>T | p.Cys4709= | synonymous_variant | 99/104 | ENST00000634891.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR3 | ENST00000634891.2 | c.14127C>T | p.Cys4709= | synonymous_variant | 99/104 | 1 | NM_001036.6 | P4 |
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, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Epileptic encephalopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 23, 2023 | - - |
RYR3-related disorder Benign:1
Likely benign, criteria provided, single submitter | 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
CADD
Benign
DANN
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at