rs2596230

chr15-33428525-T-C

Variant summary

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

The NM_001036.6(RYR3):c.52-44894T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,220 control chromosomes in the GnomAD database, including 1,014 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 0.11 (1014 hom., cov: 33)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR3	NM_001036.6	c.52-44894T>C		intron_variant		ENST00000634891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR3	ENST00000634891.2	c.52-44894T>C		intron_variant		1	NM_001036.6	P4

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17140 AN: 152102 Hom.: 1011 Cov.: 33

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0874

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0745

Gnomad FIN AF: 0.0849

Gnomad MID AF: 0.141

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.113 AC: 17161 AN: 152220 Hom.: 1014 Cov.: 33 AF XY: 0.109 AC XY: 8146 AN XY: 74438

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.0873

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0735

Gnomad4 FIN AF: 0.0849

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.122

Alfa AF: 0.111 Hom.: 1388

Bravo AF: 0.115

Asia WGS AF: 0.0450 AC: 158 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	12
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: rs2596230; hg19: chr15-33720726;