rs12148702

chr15-33636881-A-Cchr15-33636881-A-Gchr15-33636881-A-T

Variant summary

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

The NM_001036.6(RYR3):c.3556+331A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 152,202 control chromosomes in the GnomAD database, including 51,673 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 0.82 (51673 hom., cov: 33)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR3	NM_001036.6	c.3556+331A>C		intron_variant		ENST00000634891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR3	ENST00000634891.2	c.3556+331A>C		intron_variant		1	NM_001036.6	P4
RYR3	ENST00000389232.9	c.3556+331A>C		intron_variant		5		A1
RYR3	ENST00000415757.7	c.3556+331A>C		intron_variant		2		A2
RYR3	ENST00000634418.1	c.3556+331A>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.822 AC: 125034 AN: 152084 Hom.: 51618 Cov.: 33

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.938

Gnomad AMR AF: 0.846

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.869

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.826

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

GnomAD4 genome AF: 0.822 AC: 125144 AN: 152202 Hom.: 51673 Cov.: 33 AF XY: 0.820 AC XY: 61000 AN XY: 74420

Gnomad4 AFR AF: 0.782

Gnomad4 AMR AF: 0.846

Gnomad4 ASJ AF: 0.892

Gnomad4 EAS AF: 0.676

Gnomad4 SAS AF: 0.711

Gnomad4 FIN AF: 0.869

Gnomad4 NFE AF: 0.848

Gnomad4 OTH AF: 0.827

Alfa AF: 0.846 Hom.: 50941

Bravo AF: 0.821

Asia WGS AF: 0.730 AC: 2536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	14
Dann	Benign	0.75

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: rs12148702; hg19: chr15-33929082;