rs113699058

Positions:

• chr15-33696500-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001036.6(RYR3):​c.6134+9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,613,792 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0064 (8 hom., cov: 31)
  • Exomes 𝑓: 0.00091 (16 hom.)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.527

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 15-33696500-T-C is Benign according to our data. Variant chr15-33696500-T-C is described in ClinVar as [Benign]. Clinvar id is 461934.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00643 (980/152308) while in subpopulation AFR AF= 0.022 (916/41578). AF 95% confidence interval is 0.0208. There are 8 homozygotes in gnomad4. There are 464 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR3	NM_001036.6	c.6134+9T>C		intron_variant		ENST00000634891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR3	ENST00000634891.2	c.6134+9T>C		intron_variant		1	NM_001036.6	P4
RYR3	ENST00000389232.9	c.6134+9T>C		intron_variant		5		A1
RYR3	ENST00000415757.7	c.6134+9T>C		intron_variant		2		A2
RYR3	ENST00000634418.1	c.6134+9T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00636 AC: 968 AN: 152190 Hom.: 7 Cov.: 31

Gnomad AFR AF: 0.0218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00347

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00199 AC: 492 AN: 247676 Hom.: 3 AF XY: 0.00167 AC XY: 224 AN XY: 134386

Gnomad AFR exome AF: 0.0213

Gnomad AMR exome AF: 0.000551

Gnomad ASJ exome AF: 0.00230

Gnomad EAS exome AF: 0.00545

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000985

Gnomad OTH exome AF: 0.00116

GnomAD4 exome AF: 0.000907 AC: 1326 AN: 1461484 Hom.: 16 Cov.: 32 AF XY: 0.000768 AC XY: 558 AN XY: 727012

Gnomad4 AFR exome AF: 0.0253

Gnomad4 AMR exome AF: 0.000626

Gnomad4 ASJ exome AF: 0.00203

Gnomad4 EAS exome AF: 0.00373

Gnomad4 SAS exome AF: 0.000174

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000648

Gnomad4 OTH exome AF: 0.00244

GnomAD4 genome AF: 0.00643 AC: 980 AN: 152308 Hom.: 8 Cov.: 31 AF XY: 0.00623 AC XY: 464 AN XY: 74468

Gnomad4 AFR AF: 0.0220

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00348

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00653 Hom.: 3

Bravo AF: 0.00740

Asia WGS AF: 0.00722 AC: 25 AN: 3478

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

Oct 03, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.54
DANN	Benign	0.24

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs113699058; hg19: chr15-33988701;