rs2596179

Positions:

• chr15-33362531-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001036.6(RYR3):​c.51+51435A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 151,928 control chromosomes in the GnomAD database, including 11,038 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (11038 hom., cov: 31)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.672

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR3	NM_001036.6	c.51+51435A>C		intron_variant		ENST00000634891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR3	ENST00000634891.2	c.51+51435A>C		intron_variant		1	NM_001036.6	P4

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57653 AN: 151810 Hom.: 11033 Cov.: 31

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.345

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.380 AC: 57700 AN: 151928 Hom.: 11038 Cov.: 31 AF XY: 0.381 AC XY: 28313 AN XY: 74264

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.561

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.345

Alfa AF: 0.368 Hom.: 5676

Bravo AF: 0.379

Asia WGS AF: 0.423 AC: 1469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.0
DANN	Benign	0.76

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: rs2596179; hg19: chr15-33654732;