rs148404688

chr15-33757613-A-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001036.6(RYR3):c.8705+17A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00711 in 1,606,702 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0050 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0073 (53 hom.)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0420

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 15-33757613-A-C is Benign according to our data. Variant chr15-33757613-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 445856.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR3	NM_001036.6	c.8705+17A>C		intron_variant		ENST00000634891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR3	ENST00000634891.2	c.8705+17A>C		intron_variant		1	NM_001036.6	P4

Frequencies

GnomAD3 genomes AF: 0.00497 AC: 756 AN: 152118 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00147

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00622

Gnomad FIN AF: 0.00452

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00820

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00519 AC: 1225 AN: 236164 Hom.: 10 AF XY: 0.00556 AC XY: 709 AN XY: 127540

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.000782

Gnomad ASJ exome AF: 0.000308

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00610

Gnomad FIN exome AF: 0.00453

Gnomad NFE exome AF: 0.00834

Gnomad OTH exome AF: 0.00292

GnomAD4 exome AF: 0.00733 AC: 10661 AN: 1454468 Hom.: 53 Cov.: 31 AF XY: 0.00718 AC XY: 5187 AN XY: 722498

Gnomad4 AFR exome AF: 0.00108

Gnomad4 AMR exome AF: 0.000685

Gnomad4 ASJ exome AF: 0.000771

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00582

Gnomad4 FIN exome AF: 0.00579

Gnomad4 NFE exome AF: 0.00857

Gnomad4 OTH exome AF: 0.00444

GnomAD4 genome AF: 0.00498 AC: 758 AN: 152234 Hom.: 4 Cov.: 32 AF XY: 0.00496 AC XY: 369 AN XY: 74432

Gnomad4 AFR AF: 0.00147

Gnomad4 AMR AF: 0.00163

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00664

Gnomad4 FIN AF: 0.00452

Gnomad4 NFE AF: 0.00820

Gnomad4 OTH AF: 0.00427

Alfa AF: 0.00509 Hom.: 0

Bravo AF: 0.00425

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Aug 02, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.4
Dann	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs148404688; hg19: chr15-34049814;