rs1979738

chr15-33658527-A-G

Variant summary

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

The NM_001036.6(RYR3):c.4309-1193A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 152,178 control chromosomes in the GnomAD database, including 25,924 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 0.55 (25924 hom., cov: 33)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.792

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR3	NM_001036.6	c.4309-1193A>G		intron_variant		ENST00000634891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR3	ENST00000634891.2	c.4309-1193A>G		intron_variant		1	NM_001036.6	P4
RYR3	ENST00000389232.9	c.4309-1193A>G		intron_variant		5		A1
RYR3	ENST00000415757.7	c.4309-1193A>G		intron_variant		2		A2
RYR3	ENST00000634418.1	c.4309-1193A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83416 AN: 152060 Hom.: 25914 Cov.: 33

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.548 AC: 83449 AN: 152178 Hom.: 25924 Cov.: 33 AF XY: 0.556 AC XY: 41366 AN XY: 74416

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.605

Gnomad4 ASJ AF: 0.591

Gnomad4 EAS AF: 0.585

Gnomad4 SAS AF: 0.605

Gnomad4 FIN AF: 0.778

Gnomad4 NFE AF: 0.676

Gnomad4 OTH AF: 0.557

Alfa AF: 0.647 Hom.: 42633

Bravo AF: 0.524

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.9
Dann	Benign	0.70

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: rs1979738; hg19: chr15-33950728;