chr15-33692647-C-T

Variant names:

• chr15-33692647-C-T
• rs1353348
• NM_001036.6:c.5861-3571C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.95).
• 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 rank	MANE	Protein	UniProt
RYR3	NM_001036.6	c.5861-3571C>T		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.5861-3571C>T		intron_variant	Intron 38 of 103	1	NM_001036.6	ENSP00000489262.1
RYR3	ENST00000389232.9	c.5861-3571C>T		intron_variant	Intron 38 of 103	5		ENSP00000373884.5
RYR3	ENST00000415757.7	c.5861-3571C>T		intron_variant	Intron 38 of 102	2		ENSP00000399610.3
RYR3	ENST00000634418.1	c.5861-3571C>T		intron_variant	Intron 38 of 101	5		ENSP00000489529.1

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

African (AFR) AF: 0.298 AC: 12023 AN: 40350

American (AMR) AF: 0.677 AC: 10169 AN: 15028

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 2162 AN: 3454

East Asian (EAS) AF: 0.722 AC: 3660 AN: 5070

South Asian (SAS) AF: 0.737 AC: 3459 AN: 4694

European-Finnish (FIN) AF: 0.698 AC: 6819 AN: 9768

Middle Eastern (MID) AF: 0.621 AC: 180 AN: 290

European-Non Finnish (NFE) AF: 0.704 AC: 47627 AN: 67608

Other (OTH) AF: 0.591 AC: 1216 AN: 2058

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
PhyloP100		-0.81
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: rs1353348; hg19: chr15-33984848;