rs2229118
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001036.6(RYR3):c.2502T>A(p.Ile834=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00977 in 1,613,934 control chromosomes in the GnomAD database, including 1,122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.048 ( 592 hom., cov: 33)
Exomes 𝑓: 0.0058 ( 530 hom. )
Consequence
RYR3
NM_001036.6 synonymous
NM_001036.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.06
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
Variant 15-33623951-T-A is Benign according to our data. Variant chr15-33623951-T-A is described in ClinVar as [Benign]. Clinvar id is 461892.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.06 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR3 | NM_001036.6 | c.2502T>A | p.Ile834= | synonymous_variant | 20/104 | ENST00000634891.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR3 | ENST00000634891.2 | c.2502T>A | p.Ile834= | synonymous_variant | 20/104 | 1 | NM_001036.6 | P4 | |
RYR3 | ENST00000389232.9 | c.2502T>A | p.Ile834= | synonymous_variant | 20/104 | 5 | A1 | ||
RYR3 | ENST00000415757.7 | c.2502T>A | p.Ile834= | synonymous_variant | 20/103 | 2 | A2 | ||
RYR3 | ENST00000634418.1 | c.2502T>A | p.Ile834= | synonymous_variant | 20/102 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0482 AC: 7332AN: 152140Hom.: 588 Cov.: 33
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GnomAD3 exomes AF: 0.0142 AC: 3529AN: 249072Hom.: 232 AF XY: 0.0112 AC XY: 1516AN XY: 135120
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GnomAD4 exome AF: 0.00575 AC: 8409AN: 1461676Hom.: 530 Cov.: 32 AF XY: 0.00508 AC XY: 3696AN XY: 727122
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GnomAD4 genome AF: 0.0483 AC: 7357AN: 152258Hom.: 592 Cov.: 33 AF XY: 0.0450 AC XY: 3347AN XY: 74454
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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 | Labcorp Genetics (formerly Invitae), Labcorp | Jan 17, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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