chr15-33680306-G-A

Variant names:

• chr15-33680306-G-A
• rs4779632
• NM_001036.6:c.5860+9750G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001036.6(RYR3):​c.5860+9750G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 152,172 control chromosomes in the GnomAD database, including 53,480 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 0.83 (53480 hom., cov: 33)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.288
• Publications: 4 publications found

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]

RYR3 Gene-Disease associations (from GenCC):

• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen, G2P
• congenital myopathy

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RYR3	NM_001036.6	c.5860+9750G>A		intron_variant	Intron 38 of 103	ENST00000634891.2	NP_001027.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RYR3	ENST00000634891.2	c.5860+9750G>A		intron_variant	Intron 38 of 103	1	NM_001036.6	ENSP00000489262.1
RYR3	ENST00000389232.9	c.5860+9750G>A		intron_variant	Intron 38 of 103	5		ENSP00000373884.5
RYR3	ENST00000415757.7	c.5860+9750G>A		intron_variant	Intron 38 of 102	2		ENSP00000399610.3
RYR3	ENST00000634418.1	c.5860+9750G>A		intron_variant	Intron 38 of 101	5		ENSP00000489529.1

Frequencies

GnomAD3 genomes AF: 0.835 AC: 126933 AN: 152054 Hom.: 53429 Cov.: 33

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.927

Gnomad AMR AF: 0.904

Gnomad ASJ AF: 0.853

Gnomad EAS AF: 0.896

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.862

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.885

Gnomad OTH AF: 0.843

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

GnomAD4 genome AF: 0.835 AC: 127039 AN: 152172 Hom.: 53480 Cov.: 33 AF XY: 0.836 AC XY: 62208 AN XY: 74412

African (AFR) AF: 0.710 AC: 29448 AN: 41456

American (AMR) AF: 0.904 AC: 13834 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.853 AC: 2963 AN: 3472

East Asian (EAS) AF: 0.896 AC: 4634 AN: 5172

South Asian (SAS) AF: 0.823 AC: 3974 AN: 4826

European-Finnish (FIN) AF: 0.862 AC: 9143 AN: 10604

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.885 AC: 60172 AN: 68022

Other (OTH) AF: 0.839 AC: 1776 AN: 2116

Alfa AF: 0.870 Hom.: 103691

Bravo AF: 0.838

Asia WGS AF: 0.838 AC: 2914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.87
DANN	Benign	0.70
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4779632; hg19: chr15-33972507;