15-33692647-C-T

Position:

• chr15-33692647-C-T

Variant summary

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

The NM_001036.6(RYR3):​c.5861-3571C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 149,226 control chromosomes in the GnomAD database, including 28,237 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 0.59 (28237 hom., cov: 25)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.813

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR3	NM_001036.6	c.5861-3571C>T		intron_variant		ENST00000634891.2	NP_001027.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYR3	ENST00000634891.2	c.5861-3571C>T		intron_variant		1	NM_001036.6	ENSP00000489262	P4
RYR3	ENST00000389232.9	c.5861-3571C>T		intron_variant		5		ENSP00000373884	A1
RYR3	ENST00000415757.7	c.5861-3571C>T		intron_variant		2		ENSP00000399610	A2
RYR3	ENST00000634418.1	c.5861-3571C>T		intron_variant		5		ENSP00000489529

Frequencies

GnomAD3 genomes AF: 0.590 AC: 87911 AN: 149126 Hom.: 28229 Cov.: 25

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.687

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.609

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.592

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

GnomAD4 genome AF: 0.589 AC: 87937 AN: 149226 Hom.: 28237 Cov.: 25 AF XY: 0.594 AC XY: 43154 AN XY: 72612

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.677

Gnomad4 ASJ AF: 0.626

Gnomad4 EAS AF: 0.722

Gnomad4 SAS AF: 0.737

Gnomad4 FIN AF: 0.698

Gnomad4 NFE AF: 0.704

Gnomad4 OTH AF: 0.591

Alfa AF: 0.628 Hom.: 4233

Bravo AF: 0.574

Asia WGS AF: 0.664 AC: 2307 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.42
DANN	Benign	0.54

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: rs1353348; hg19: chr15-33984848;