rs575029619
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_001036.6(RYR3):c.9589+6G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000261 in 1,545,282 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00027 ( 1 hom. )
Consequence
RYR3
NM_001036.6 splice_donor_region, intron
NM_001036.6 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.0001532
2
Clinical Significance
Conservation
PhyloP100: -0.158
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 Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
Variant 15-33785988-G-A is Benign according to our data. Variant chr15-33785988-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 531085.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR3 | NM_001036.6 | c.9589+6G>A | splice_donor_region_variant, intron_variant | ENST00000634891.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR3 | ENST00000634891.2 | c.9589+6G>A | splice_donor_region_variant, intron_variant | 1 | NM_001036.6 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152128Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000494 AC: 97AN: 196544Hom.: 1 AF XY: 0.000650 AC XY: 68AN XY: 104614
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GnomAD4 exome AF: 0.000273 AC: 380AN: 1393036Hom.: 1 Cov.: 30 AF XY: 0.000390 AC XY: 267AN XY: 684044
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GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152246Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74446
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Epileptic encephalopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 06, 2022 | - - |
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
Find out detailed SpliceAI scores and Pangolin per-transcript scores at