rs182429820
Positions:
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2
The NM_001036.6(RYR3):c.2574+3A>C variant causes a splice donor region, intron change. The variant allele was found at a frequency of 0.000557 in 1,610,488 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00081 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00053 ( 3 hom. )
Consequence
RYR3
NM_001036.6 splice_donor_region, intron
NM_001036.6 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.4816
2
Clinical Significance
Conservation
PhyloP100: 5.73
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 -8 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
?
Variant 15-33624026-A-C is Benign according to our data. Variant chr15-33624026-A-C is described in ClinVar as [Benign]. Clinvar id is 461894.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High Homozygotes in GnomAdExome4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR3 | NM_001036.6 | c.2574+3A>C | splice_donor_region_variant, intron_variant | ENST00000634891.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR3 | ENST00000634891.2 | c.2574+3A>C | splice_donor_region_variant, intron_variant | 1 | NM_001036.6 | P4 | |||
RYR3 | ENST00000389232.9 | c.2574+3A>C | splice_donor_region_variant, intron_variant | 5 | A1 | ||||
RYR3 | ENST00000415757.7 | c.2574+3A>C | splice_donor_region_variant, intron_variant | 2 | A2 | ||||
RYR3 | ENST00000634418.1 | c.2574+3A>C | splice_donor_region_variant, intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000808 AC: 123AN: 152260Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00148 AC: 367AN: 248042Hom.: 1 AF XY: 0.00140 AC XY: 188AN XY: 134546
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GnomAD4 exome AF: 0.000531 AC: 774AN: 1458110Hom.: 3 Cov.: 30 AF XY: 0.000531 AC XY: 385AN XY: 725472
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GnomAD4 genome ? AF: 0.000807 AC: 123AN: 152378Hom.: 0 Cov.: 33 AF XY: 0.00101 AC XY: 75AN XY: 74514
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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 | Aug 04, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: -3
Find out detailed SpliceAI scores and Pangolin per-transcript scores at