rs199645058
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_001036.6(RYR3):āc.13938A>Gā(p.Leu4646=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000163 in 1,613,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00082 ( 0 hom., cov: 32)
Exomes š: 0.000094 ( 0 hom. )
Consequence
RYR3
NM_001036.6 synonymous
NM_001036.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.152
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 -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
Variant 15-33854843-A-G is Benign according to our data. Variant chr15-33854843-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 531104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.152 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR3 | NM_001036.6 | c.13938A>G | p.Leu4646= | synonymous_variant | 98/104 | ENST00000634891.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR3 | ENST00000634891.2 | c.13938A>G | p.Leu4646= | synonymous_variant | 98/104 | 1 | NM_001036.6 | P4 | |
ENST00000560404.2 | n.600T>C | splice_region_variant, non_coding_transcript_exon_variant | 2/3 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000822 AC: 125AN: 152066Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000237 AC: 59AN: 249118Hom.: 0 AF XY: 0.000170 AC XY: 23AN XY: 135144
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GnomAD4 exome AF: 0.0000944 AC: 138AN: 1461622Hom.: 0 Cov.: 32 AF XY: 0.0000701 AC XY: 51AN XY: 727082
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GnomAD4 genome ? AF: 0.000821 AC: 125AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.000766 AC XY: 57AN XY: 74408
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ClinVar
Significance: Benign/Likely 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 | Aug 22, 2022 | - - |
RYR3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 03, 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
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