Variant rs75782410 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001036.6(RYR3):c.2164+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0236 in 1,549,158 control chromosomes in the GnomAD database, including 519 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 32 hom., cov: 31)

Exomes 𝑓: 0.024 ( 487 hom. )

Consequence

RYR3
NM_001036.6 splice_region, intron

Scores

Splicing: ADA: 0.00006225

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.720

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 15-33603372-C-T is Benign according to our data. Variant chr15-33603372-C-T is described in ClinVar as [Benign]. Clinvar id is 461888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-33603372-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0173 (2635/152220) while in subpopulation NFE AF= 0.0262 (1785/68018). AF 95% confidence interval is 0.0252. There are 32 homozygotes in gnomad4. There are 1259 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR3	NM_001036.6 linkuse as main transcript	c.2164+8C>T		splice_region_variant, intron_variant		ENST00000634891.2	NP_001027.3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
RYR3	ENST00000634891.2 linkuse as main transcript	c.2164+8C>T	splice_region_variant, intron_variant	1	NM_001036.6	ENSP00000489262	P4	Q15413-1
RYR3	ENST00000389232.9 linkuse as main transcript	c.2164+8C>T	splice_region_variant, intron_variant	5		ENSP00000373884	A1
RYR3	ENST00000415757.7 linkuse as main transcript	c.2164+8C>T	splice_region_variant, intron_variant	2		ENSP00000399610	A2	Q15413-2
RYR3	ENST00000634418.1 linkuse as main transcript	c.2164+8C>T	splice_region_variant, intron_variant	5		ENSP00000489529

Frequencies

GnomAD3 genomes

AF:

0.0173

AC:

2637

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00570

Gnomad AMI

AF:

0.0757

Gnomad AMR

AF:

0.0164

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00913

Gnomad FIN

AF:

0.0181

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0262

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.0189

AC:

3813

AN:

201828

Hom.:

AF XY:

0.0188

AC XY:

2032

AN XY:

108312

show subpopulations

Gnomad AFR exome

AF:

0.00458

Gnomad AMR exome

AF:

0.0138

Gnomad ASJ exome

AF:

0.00800

Gnomad EAS exome

AF:

0.0000604

Gnomad SAS exome

AF:

0.0120

Gnomad FIN exome

AF:

0.0207

Gnomad NFE exome

AF:

0.0274

Gnomad OTH exome

AF:

0.0196

GnomAD4 exome

AF:

0.0243

AC:

33962

AN:

1396938

Hom.:

487

Cov.:

AF XY:

0.0240

AC XY:

16510

AN XY:

688160

show subpopulations

Gnomad4 AFR exome

AF:

0.00461

Gnomad4 AMR exome

AF:

0.0132

Gnomad4 ASJ exome

AF:

0.00810

Gnomad4 EAS exome

AF:

0.000103

Gnomad4 SAS exome

AF:

0.0107

Gnomad4 FIN exome

AF:

0.0209

Gnomad4 NFE exome

AF:

0.0278

Gnomad4 OTH exome

AF:

0.0211

GnomAD4 genome

AF:

0.0173

AC:

2635

AN:

152220

Hom.:

Cov.:

AF XY:

0.0169

AC XY:

1259

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.00568

Gnomad4 AMR

AF:

0.0164

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00893

Gnomad4 FIN

AF:

0.0181

Gnomad4 NFE

AF:

0.0262

Gnomad4 OTH

AF:

0.0133

Alfa

AF:

0.0197

Hom.:

Bravo

AF:

0.0160

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Epileptic encephalopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 15, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000062

dbscSNV1_RF

Benign

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over