rs112521485
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001036.6(RYR3):c.7581C>T(p.Tyr2527=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00058 in 1,613,884 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0031 ( 7 hom., cov: 32)
Exomes 𝑓: 0.00032 ( 4 hom. )
Consequence
RYR3
NM_001036.6 synonymous
NM_001036.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.422
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 -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
BP6
Variant 15-33738515-C-T is Benign according to our data. Variant chr15-33738515-C-T is described in ClinVar as [Benign]. Clinvar id is 461951.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.422 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 7 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR3 | NM_001036.6 | c.7581C>T | p.Tyr2527= | synonymous_variant | 50/104 | ENST00000634891.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR3 | ENST00000634891.2 | c.7581C>T | p.Tyr2527= | synonymous_variant | 50/104 | 1 | NM_001036.6 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00310 AC: 472AN: 152112Hom.: 7 Cov.: 32
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GnomAD3 exomes AF: 0.000722 AC: 180AN: 249152Hom.: 0 AF XY: 0.000584 AC XY: 79AN XY: 135164
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GnomAD4 exome AF: 0.000315 AC: 461AN: 1461654Hom.: 4 Cov.: 31 AF XY: 0.000279 AC XY: 203AN XY: 727116
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GnomAD4 genome AF: 0.00312 AC: 475AN: 152230Hom.: 7 Cov.: 32 AF XY: 0.00314 AC XY: 234AN XY: 74446
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Epileptic encephalopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 03, 2023 | - - |
RYR3-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 13, 2019 | This variant is classified as 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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DANN
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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