Variant chr15-33785987-C-T details in Genebe, Genetics Data Aggregator

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+5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00036 in 1,545,776 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 1 hom. )

Consequence

RYR3
NM_001036.6 splice_region, intron

Scores

Splicing: ADA: 0.00006966

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.454

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]

RYR3 links:

RYR3 (HGNC:):

RYR3 links:

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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=-0.79).

BP6

Variant 15-33785987-C-T is Benign according to our data. Variant chr15-33785987-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 531074.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR3	NM_001036.6 linkuse as main transcript	c.9589+5C>T		splice_region_variant, intron_variant		ENST00000634891.2	NP_001027.3	Q15413-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYR3	ENST00000634891.2 linkuse as main transcript	c.9589+5C>T		splice_region_variant, intron_variant		1	NM_001036.6	ENSP00000489262.1		Q15413-1

Frequencies

GnomAD3 genomes

AF:

0.00135

AC:

206

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00384

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000671

AC:

132

AN:

196756

Hom.:

AF XY:

0.000601

AC XY:

AN XY:

104746

show subpopulations

Gnomad AFR exome

AF:

0.00423

Gnomad AMR exome

AF:

0.000150

Gnomad ASJ exome

AF:

0.000377

Gnomad EAS exome

AF:

0.0000597

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00160

Gnomad NFE exome

AF:

0.000328

Gnomad OTH exome

AF:

0.000643

GnomAD4 exome

AF:

0.000253

AC:

352

AN:

1393548

Hom.:

Cov.:

AF XY:

0.000232

AC XY:

159

AN XY:

684392

show subpopulations

Gnomad4 AFR exome

AF:

0.00333

Gnomad4 AMR exome

AF:

0.000161

Gnomad4 ASJ exome

AF:

0.000362

Gnomad4 EAS exome

AF:

0.0000258

Gnomad4 SAS exome

AF:

0.0000133

Gnomad4 FIN exome

AF:

0.00162

Gnomad4 NFE exome

AF:

0.000116

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.00135

AC:

205

AN:

152228

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

118

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00380

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000687

Hom.:

Bravo

AF:

0.00117

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Labcorp Genetics (formerly Invitae), Labcorp

Aug 04, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000070

dbscSNV1_RF

Benign

0.018

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over