rs78959515

Positions:

• chr15-33563714-T-C

Variant summary

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

The NM_001036.6(RYR3):​c.1146+704T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.071 in 152,254 control chromosomes in the GnomAD database, including 487 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 0.071 (487 hom., cov: 33)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.262

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.083 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR3	NM_001036.6	c.1146+704T>C		intron_variant		ENST00000634891.2	NP_001027.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYR3	ENST00000634891.2	c.1146+704T>C		intron_variant		1	NM_001036.6	ENSP00000489262	P4
RYR3	ENST00000389232.9	c.1146+704T>C		intron_variant		5		ENSP00000373884	A1
RYR3	ENST00000415757.7	c.1146+704T>C		intron_variant		2		ENSP00000399610	A2
RYR3	ENST00000634418.1	c.1146+704T>C		intron_variant		5		ENSP00000489529

Frequencies

GnomAD3 genomes AF: 0.0710 AC: 10804 AN: 152136 Hom.: 487 Cov.: 33

Gnomad AFR AF: 0.0488

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0537

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0689

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0848

Gnomad OTH AF: 0.0654

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

GnomAD4 genome AF: 0.0710 AC: 10812 AN: 152254 Hom.: 487 Cov.: 33 AF XY: 0.0724 AC XY: 5386 AN XY: 74440

Gnomad4 AFR AF: 0.0490

Gnomad4 AMR AF: 0.0535

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0685

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.0849

Gnomad4 OTH AF: 0.0643

Alfa AF: 0.0784 Hom.: 104

Bravo AF: 0.0653

Asia WGS AF: 0.0260 AC: 90 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.52

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: rs78959515; hg19: chr15-33855915;