rs200740143
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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):āc.4821T>Cā(p.Tyr1607=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0027 in 1,612,820 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 Likely benign (ā ā ).
Frequency
Genomes: š 0.0017 ( 0 hom., cov: 33)
Exomes š: 0.0028 ( 11 hom. )
Consequence
RYR3
NM_001036.6 synonymous
NM_001036.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.771
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=-0.52).
BP6
?
Variant 15-33662351-T-C is Benign according to our data. Variant chr15-33662351-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 461919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.771 with no splicing effect.
BS2
?
High Homozygotes in GnomAdExome4 at 11 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR3 | NM_001036.6 | c.4821T>C | p.Tyr1607= | synonymous_variant | 35/104 | ENST00000634891.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR3 | ENST00000634891.2 | c.4821T>C | p.Tyr1607= | synonymous_variant | 35/104 | 1 | NM_001036.6 | P4 | |
RYR3 | ENST00000389232.9 | c.4821T>C | p.Tyr1607= | synonymous_variant | 35/104 | 5 | A1 | ||
RYR3 | ENST00000415757.7 | c.4821T>C | p.Tyr1607= | synonymous_variant | 35/103 | 2 | A2 | ||
RYR3 | ENST00000634418.1 | c.4821T>C | p.Tyr1607= | synonymous_variant | 35/102 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00171 AC: 261AN: 152254Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00188 AC: 464AN: 246396Hom.: 1 AF XY: 0.00196 AC XY: 262AN XY: 133692
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GnomAD4 exome AF: 0.00280 AC: 4091AN: 1460448Hom.: 11 Cov.: 31 AF XY: 0.00274 AC XY: 1991AN XY: 726362
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GnomAD4 genome ? AF: 0.00171 AC: 261AN: 152372Hom.: 0 Cov.: 33 AF XY: 0.00149 AC XY: 111AN XY: 74512
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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 | Dec 02, 2022 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2023 | RYR3: BP4, BP7 - |
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