Variant 6-33670361-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2

The NM_002224.4(ITPR3):c.2226C>T(p.Asp742Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000521 in 1,614,120 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 3 hom. )

Consequence

ITPR3
NM_002224.4 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.13

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 6-33670361-C-T is Benign according to our data. Variant chr6-33670361-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3052627.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-33670361-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=2.13 with no splicing effect.

BS2

High AC in GnomAd4 at 229 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPR3	NM_002224.4 linkuse as main transcript	c.2226C>T	p.Asp742Asp	synonymous_variant	19/58	ENST00000605930.3	NP_002215.2	Q14573A6H8K3Q59ES2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPR3	ENST00000605930.3 linkuse as main transcript	c.2226C>T	p.Asp742Asp	synonymous_variant	19/58	1	NM_002224.4	ENSP00000475177.1		Q14573
ITPR3	ENST00000374316.9 linkuse as main transcript	c.2226C>T	p.Asp742Asp	synonymous_variant	20/59	5		ENSP00000363435.4		Q14573

Frequencies

GnomAD3 genomes

AF:

0.00150

AC:

228

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00490

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000594

AC:

149

AN:

250868

Hom.:

AF XY:

0.000457

AC XY:

AN XY:

135642

show subpopulations

Gnomad AFR exome

AF:

0.00640

Gnomad AMR exome

AF:

0.000520

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:

0.000203

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000419

AC:

612

AN:

1461798

Hom.:

Cov.:

AF XY:

0.000385

AC XY:

280

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.00786

Gnomad4 AMR exome

AF:

0.000671

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000258

Gnomad4 OTH exome

AF:

0.000480

GnomAD4 genome

AF:

0.00150

AC:

229

AN:

152322

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

113

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00488

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00000552

Hom.:

Bravo

AF:

0.00181

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ITPR3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 05, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.59

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