rs199960256

chr15-33563010-G-Achr15-33563010-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001036.6(RYR3):c.1146G>A(p.Lys382=) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.000232 in 1,606,722 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00026 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (1 hom.)
• Consequence: RYR3 NM_001036.6 splice_region, synonymous
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.53

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 15-33563010-G-A is Benign according to our data. Variant chr15-33563010-G-A is described in ClinVar as [Benign]. Clinvar id is 531044.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.1146G>A	p.Lys382=	splice_region_variant, synonymous_variant	11/104	ENST00000634891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR3	ENST00000634891.2	c.1146G>A	p.Lys382=	splice_region_variant, synonymous_variant	11/104	1	NM_001036.6	P4
RYR3	ENST00000389232.9	c.1146G>A	p.Lys382=	splice_region_variant, synonymous_variant	11/104	5		A1
RYR3	ENST00000415757.7	c.1146G>A	p.Lys382=	splice_region_variant, synonymous_variant	11/103	2		A2
RYR3	ENST00000634418.1	c.1146G>A	p.Lys382=	splice_region_variant, synonymous_variant	11/102	5

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 40 AN: 152134 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00894

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.000431 AC: 105 AN: 243886 Hom.: 0 AF XY: 0.000447 AC XY: 59 AN XY: 132108

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00932

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000989

Gnomad OTH exome AF: 0.000339

GnomAD4 exome AF: 0.000229 AC: 333 AN: 1454588 Hom.: 1 Cov.: 30 AF XY: 0.000252 AC XY: 182 AN XY: 722564

Gnomad4 AFR exome AF: 0.0000302

Gnomad4 AMR exome AF: 0.0000229

Gnomad4 ASJ exome AF: 0.00905

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000379

Gnomad4 OTH exome AF: 0.000898

GnomAD4 genome AF: 0.000263 AC: 40 AN: 152134 Hom.: 1 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74318

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00894

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00144

Alfa AF: 0.000580 Hom.: 0

Bravo AF: 0.000272

EpiCase AF: 0.000219

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Epileptic encephalopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 04, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.18
Cadd	Benign	20
Dann	Benign	0.88

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	1.0
SpliceAI score (max)		0.38		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.38		Position offset: 0

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

Publications

LitVar

Other links and lift over

dbSNP: rs199960256; hg19: chr15-33855211;