rs597566

chr15-33592422-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.1788+6306A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 152,038 control chromosomes in the GnomAD database, including 36,252 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 0.69 (36252 hom., cov: 31)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.363

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR3	NM_001036.6	c.1788+6306A>T		intron_variant		ENST00000634891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR3	ENST00000634891.2	c.1788+6306A>T		intron_variant		1	NM_001036.6	P4
RYR3	ENST00000389232.9	c.1788+6306A>T		intron_variant		5		A1
RYR3	ENST00000415757.7	c.1788+6306A>T		intron_variant		2		A2
RYR3	ENST00000634418.1	c.1788+6306A>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104191 AN: 151920 Hom.: 36220 Cov.: 31

Gnomad AFR AF: 0.812

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.645

Gnomad OTH AF: 0.653

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

GnomAD4 genome AF: 0.686 AC: 104279 AN: 152038 Hom.: 36252 Cov.: 31 AF XY: 0.679 AC XY: 50502 AN XY: 74328

Gnomad4 AFR AF: 0.811

Gnomad4 AMR AF: 0.615

Gnomad4 ASJ AF: 0.661

Gnomad4 EAS AF: 0.764

Gnomad4 SAS AF: 0.579

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.645

Gnomad4 OTH AF: 0.653

Alfa AF: 0.671 Hom.: 4282

Bravo AF: 0.693

Asia WGS AF: 0.682 AC: 2372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.81
Dann	Benign	0.35

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: rs597566; hg19: chr15-33884623;