Variant chr15-33859700-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001036.6(RYR3):c.14268C>T(p.Phe4756=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0373 in 1,611,940 control chromosomes in the GnomAD database, including 1,484 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 157 hom., cov: 32)

Exomes 𝑓: 0.038 ( 1327 hom. )

Consequence

RYR3
NM_001036.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.229

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:

(HGNC:):

links:

AVEN (HGNC:13509): (apoptosis and caspase activation inhibitor) Involved in negative regulation of apoptotic process. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

AVEN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 15-33859700-C-T is Benign according to our data. Variant chr15-33859700-C-T is described in ClinVar as [Benign]. Clinvar id is 461877.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-33859700-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.229 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0326 (4958/152212) while in subpopulation NFE AF= 0.039 (2655/67998). AF 95% confidence interval is 0.0378. There are 157 homozygotes in gnomad4. There are 2657 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 157 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR3	NM_001036.6 linkuse as main transcript	c.14268C>T	p.Phe4756=	synonymous_variant	100/104	ENST00000634891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR3	ENST00000634891.2 linkuse as main transcript	c.14268C>T	p.Phe4756=	synonymous_variant	100/104	1	NM_001036.6	P4	Q15413-1
	ENST00000560268.2 linkuse as main transcript	n.70-606G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0326

AC:

4961

AN:

152094

Hom.:

157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0300

Gnomad ASJ

AF:

0.0331

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0120

Gnomad FIN

AF:

0.124

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0391

Gnomad OTH

AF:

0.0263

GnomAD3 exomes

AF:

0.0356

AC:

8741

AN:

245636

Hom.:

276

AF XY:

0.0362

AC XY:

4814

AN XY:

133140

show subpopulations

Gnomad AFR exome

AF:

0.00713

Gnomad AMR exome

AF:

0.0221

Gnomad ASJ exome

AF:

0.0305

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0132

Gnomad FIN exome

AF:

0.115

Gnomad NFE exome

AF:

0.0399

Gnomad OTH exome

AF:

0.0474

GnomAD4 exome

AF:

0.0378

AC:

55211

AN:

1459728

Hom.:

1327

Cov.:

AF XY:

0.0369

AC XY:

26799

AN XY:

725930

show subpopulations

Gnomad4 AFR exome

AF:

0.00538

Gnomad4 AMR exome

AF:

0.0227

Gnomad4 ASJ exome

AF:

0.0314

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0144

Gnomad4 FIN exome

AF:

0.110

Gnomad4 NFE exome

AF:

0.0395

Gnomad4 OTH exome

AF:

0.0351

GnomAD4 genome

AF:

0.0326

AC:

4958

AN:

152212

Hom.:

157

Cov.:

AF XY:

0.0357

AC XY:

2657

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00722

Gnomad4 AMR

AF:

0.0299

Gnomad4 ASJ

AF:

0.0331

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0118

Gnomad4 FIN

AF:

0.124

Gnomad4 NFE

AF:

0.0390

Gnomad4 OTH

AF:

0.0265

Alfa

AF:

0.0340

Hom.:

Bravo

AF:

0.0260

Asia WGS

AF:

0.00606

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

-0.29

CADD

Benign

4.1

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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