rs183255287

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000634891.2(RYR3):​c.5419-8C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000385 in 1,612,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

RYR3
ENST00000634891.2 splice_region, splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.002949
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.443
Variant links:
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]

Genome browser will be placed here

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=-0.83).
BP6
Variant 15-33663529-C-G is Benign according to our data. Variant chr15-33663529-C-G is described in ClinVar as [Benign]. Clinvar id is 531154.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RYR3NM_001036.6 linkuse as main transcriptc.5419-8C>G splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000634891.2 NP_001027.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RYR3ENST00000634891.2 linkuse as main transcriptc.5419-8C>G splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 NM_001036.6 ENSP00000489262 P4Q15413-1
RYR3ENST00000389232.9 linkuse as main transcriptc.5419-8C>G splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 5 ENSP00000373884 A1
RYR3ENST00000415757.7 linkuse as main transcriptc.5419-8C>G splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 2 ENSP00000399610 A2Q15413-2
RYR3ENST00000634418.1 linkuse as main transcriptc.5419-8C>G splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 5 ENSP00000489529

Frequencies

GnomAD3 genomes
AF:
0.0000788
AC:
12
AN:
152212
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00231
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000154
AC:
38
AN:
246130
Hom.:
0
AF XY:
0.000120
AC XY:
16
AN XY:
133556
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00207
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000166
GnomAD4 exome
AF:
0.0000343
AC:
50
AN:
1459822
Hom.:
0
Cov.:
31
AF XY:
0.0000303
AC XY:
22
AN XY:
725980
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00111
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000995
GnomAD4 genome
AF:
0.0000788
AC:
12
AN:
152330
Hom.:
0
Cov.:
32
AF XY:
0.0000805
AC XY:
6
AN XY:
74492
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00231
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000604
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJun 13, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
0.66
DANN
Benign
0.42

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0029
dbscSNV1_RF
Benign
0.048
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs183255287; hg19: chr15-33955730; API