Variant 6-33657919-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_002224.4(ITPR3):c.283-13T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,611,136 control chromosomes in the GnomAD database, including 45,897 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.20 ( 3762 hom., cov: 31)

Exomes 𝑓: 0.23 ( 42135 hom. )

Consequence

ITPR3
NM_002224.4 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.194

Variant links:

Genes affected

ITPR3 (HGNC:6182): (inositol 1,4,5-trisphosphate receptor type 3) This gene encodes a receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium. The receptor contains a calcium channel at the C-terminus and the ligand-binding site at the N-terminus. Knockout studies in mice suggest that type 2 and type 3 inositol 1,4,5-trisphosphate receptors play a key role in exocrine secretion underlying energy metabolism and growth. [provided by RefSeq, Aug 2010]

ITPR3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 6-33657919-T-C is Benign according to our data. Variant chr6-33657919-T-C is described in ClinVar as [Benign]. Clinvar id is 1251103.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITPR3	NM_002224.4 linkuse as main transcript	c.283-13T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000605930.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPR3	ENST00000605930.3 linkuse as main transcript	c.283-13T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002224.4	P1
ITPR3	ENST00000374316.9 linkuse as main transcript	c.283-13T>C		splice_polypyrimidine_tract_variant, intron_variant		5		P1

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30764

AN:

151790

Hom.:

3765

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0641

Gnomad AMI

AF:

0.242

Gnomad AMR

AF:

0.255

Gnomad ASJ

AF:

0.284

Gnomad EAS

AF:

0.280

Gnomad SAS

AF:

0.294

Gnomad FIN

AF:

0.351

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.236

Gnomad OTH

AF:

0.174

GnomAD3 exomes

AF:

0.257

AC:

64141

AN:

249106

Hom.:

8932

AF XY:

0.260

AC XY:

34996

AN XY:

134664

show subpopulations

Gnomad AFR exome

AF:

0.0580

Gnomad AMR exome

AF:

0.329

Gnomad ASJ exome

AF:

0.267

Gnomad EAS exome

AF:

0.291

Gnomad SAS exome

AF:

0.279

Gnomad FIN exome

AF:

0.343

Gnomad NFE exome

AF:

0.237

Gnomad OTH exome

AF:

0.247

GnomAD4 exome

AF:

0.235

AC:

342860

AN:

1459228

Hom.:

42135

Cov.:

AF XY:

0.238

AC XY:

172447

AN XY:

725908

show subpopulations

Gnomad4 AFR exome

AF:

0.0552

Gnomad4 AMR exome

AF:

0.319

Gnomad4 ASJ exome

AF:

0.267

Gnomad4 EAS exome

AF:

0.263

Gnomad4 SAS exome

AF:

0.284

Gnomad4 FIN exome

AF:

0.336

Gnomad4 NFE exome

AF:

0.227

Gnomad4 OTH exome

AF:

0.224

GnomAD4 genome

AF:

0.203

AC:

30762

AN:

151908

Hom.:

3762

Cov.:

AF XY:

0.211

AC XY:

15639

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.0639

Gnomad4 AMR

AF:

0.254

Gnomad4 ASJ

AF:

0.284

Gnomad4 EAS

AF:

0.281

Gnomad4 SAS

AF:

0.295

Gnomad4 FIN

AF:

0.351

Gnomad4 NFE

AF:

0.236

Gnomad4 OTH

AF:

0.173

Alfa

AF:

0.225

Hom.:

4025

Bravo

AF:

0.188

Asia WGS

AF:

0.220

AC:

767

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.36

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.36

Position offset: -33

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