Variant rs41279216 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001036.6(RYR3):c.8136+9C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00403 in 1,613,344 control chromosomes in the GnomAD database, including 245 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 126 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 119 hom. )

Consequence

RYR3
NM_001036.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.15

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 15-33748269-C-G is Benign according to our data. Variant chr15-33748269-C-G is described in ClinVar as [Benign]. Clinvar id is 461965.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR3	NM_001036.6 linkuse as main transcript	c.8136+9C>G		intron_variant		ENST00000634891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR3	ENST00000634891.2 linkuse as main transcript	c.8136+9C>G		intron_variant		1	NM_001036.6	P4	Q15413-1

Frequencies

GnomAD3 genomes

AF:

0.0220

AC:

3340

AN:

152162

Hom.:

128

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0766

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00779

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.00577

AC:

1429

AN:

247760

Hom.:

AF XY:

0.00437

AC XY:

588

AN XY:

134476

show subpopulations

Gnomad AFR exome

AF:

0.0814

Gnomad AMR exome

AF:

0.00431

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000116

Gnomad OTH exome

AF:

0.00250

GnomAD4 exome

AF:

0.00216

AC:

3162

AN:

1461064

Hom.:

119

Cov.:

AF XY:

0.00183

AC XY:

1329

AN XY:

726786

show subpopulations

Gnomad4 AFR exome

AF:

0.0762

Gnomad4 AMR exome

AF:

0.00486

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000837

Gnomad4 OTH exome

AF:

0.00462

GnomAD4 genome

AF:

0.0220

AC:

3347

AN:

152280

Hom.:

126

Cov.:

AF XY:

0.0211

AC XY:

1573

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0765

Gnomad4 AMR

AF:

0.00778

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.0165

Alfa

AF:

0.00113

Hom.:

Bravo

AF:

0.0250

Asia WGS

AF:

0.00318

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

Invitae

Jan 15, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

3.2

DANN

Benign

0.60

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

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