rs9806592

chr15-33621734-A-Gchr15-33621734-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.2358-2073A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0663 in 152,212 control chromosomes in the GnomAD database, including 383 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 0.066 (383 hom., cov: 32)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.08

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR3	NM_001036.6	c.2358-2073A>G		intron_variant		ENST00000634891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR3	ENST00000634891.2	c.2358-2073A>G		intron_variant		1	NM_001036.6	P4
RYR3	ENST00000389232.9	c.2358-2073A>G		intron_variant		5		A1
RYR3	ENST00000415757.7	c.2358-2073A>G		intron_variant		2		A2
RYR3	ENST00000634418.1	c.2358-2073A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0664 AC: 10097 AN: 152094 Hom.: 382 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0187

Gnomad AMR AF: 0.0568

Gnomad ASJ AF: 0.0276

Gnomad EAS AF: 0.0847

Gnomad SAS AF: 0.0585

Gnomad FIN AF: 0.0531

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0473

Gnomad OTH AF: 0.0698

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

GnomAD4 genome AF: 0.0663 AC: 10098 AN: 152212 Hom.: 383 Cov.: 32 AF XY: 0.0664 AC XY: 4940 AN XY: 74418

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0570

Gnomad4 ASJ AF: 0.0276

Gnomad4 EAS AF: 0.0848

Gnomad4 SAS AF: 0.0588

Gnomad4 FIN AF: 0.0531

Gnomad4 NFE AF: 0.0472

Gnomad4 OTH AF: 0.0700

Alfa AF: 0.0479 Hom.: 205

Bravo AF: 0.0691

Asia WGS AF: 0.0800 AC: 278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	8.0
Dann	Benign	0.57

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: rs9806592; hg19: chr15-33913935;