rs58745096
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2
The NM_001036.6(RYR3):c.10719C>T(p.Asp3573=) 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 1,539,658 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.014 ( 65 hom., cov: 32)
Exomes 𝑓: 0.0015 ( 42 hom. )
Consequence
RYR3
NM_001036.6 synonymous
NM_001036.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.460
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 -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
?
Variant 15-33819768-C-T is Benign according to our data. Variant chr15-33819768-C-T is described in ClinVar as [Benign]. Clinvar id is 461829.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.46 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.014 (2128/152210) while in subpopulation AFR AF= 0.0482 (2003/41516). AF 95% confidence interval is 0.0465. There are 65 homozygotes in gnomad4. There are 1022 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 65 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR3 | NM_001036.6 | c.10719C>T | p.Asp3573= | synonymous_variant | 77/104 | ENST00000634891.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR3 | ENST00000634891.2 | c.10719C>T | p.Asp3573= | synonymous_variant | 77/104 | 1 | NM_001036.6 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0139 AC: 2118AN: 152092Hom.: 65 Cov.: 32
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GnomAD3 exomes AF: 0.00300 AC: 706AN: 235092Hom.: 18 AF XY: 0.00204 AC XY: 262AN XY: 128144
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GnomAD4 exome AF: 0.00146 AC: 2026AN: 1387448Hom.: 42 Cov.: 29 AF XY: 0.00124 AC XY: 850AN XY: 687516
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GnomAD4 genome ? AF: 0.0140 AC: 2128AN: 152210Hom.: 65 Cov.: 32 AF XY: 0.0137 AC XY: 1022AN XY: 74432
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Epileptic encephalopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2023 | - - |
Computational scores
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Name
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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