Genetic Variant ITPR3:c.282+14_282+15dupTG (chr6-33655890-A-ATG) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The ENST00000605930.3(ITPR3):c.282+3_282+4insTG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,613,244 control chromosomes in the GnomAD database, including 19 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 14 hom. )

Consequence

ITPR3
ENST00000605930.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.480

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP6

Variant 6-33655890-A-ATG is Benign according to our data. Variant chr6-33655890-A-ATG is described in ClinVar as [Likely_benign]. Clinvar id is 1170819.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 603 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR3	NM_002224.4 link	c.282+14_282+15dupTG		intron_variant	Intron 3 of 57	ENST00000605930.3	NP_002215.2	Q14573A6H8K3Q59ES2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPR3	ENST00000605930.3 link	c.282+3_282+4insTG		splice_region_variant, intron_variant	Intron 3 of 57	1	NM_002224.4	ENSP00000475177.1		Q14573
ITPR3	ENST00000374316.9 link	c.282+3_282+4insTG		splice_region_variant, intron_variant	Intron 4 of 58	5		ENSP00000363435.4		Q14573

Frequencies

GnomAD3 genomes

AF:

0.00383

AC:

582

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00925

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000771

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00163

Gnomad OTH

AF:

0.00669

GnomAD2 exomes

AF:

0.00243

AC:

607

AN:

249674

AF XY:

0.00244

show subpopulations

Gnomad AFR exome

AF:

0.00968

Gnomad AMR exome

AF:

0.00296

Gnomad ASJ exome

AF:

0.00130

Gnomad EAS exome

AF:

0.000708

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.00163

Gnomad OTH exome

AF:

0.00377

GnomAD4 exome

AF:

0.00163

AC:

2382

AN:

1461048

Hom.:

Cov.:

AF XY:

0.00167

AC XY:

1211

AN XY:

726840

show subpopulations

Gnomad4 AFR exome

AF:

0.00855

AC:

286

AN:

33468

Gnomad4 AMR exome

AF:

0.00300

AC:

134

AN:

44710

Gnomad4 ASJ exome

AF:

0.00103

AC:

AN:

26112

Gnomad4 EAS exome

AF:

0.000378

AC:

AN:

39670

Gnomad4 SAS exome

AF:

0.00383

AC:

330

AN:

86242

Gnomad4 FIN exome

AF:

0.0000563

AC:

AN:

53266

Gnomad4 NFE exome

AF:

0.00120

AC:

1330

AN:

1111466

Gnomad4 Remaining exome

AF:

0.00283

AC:

171

AN:

60350

Heterozygous variant carriers

118

236

353

471

589

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00396

AC:

603

AN:

152196

Hom.:

Cov.:

AF XY:

0.00414

AC XY:

308

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00975

AC:

0.00975058

AN:

0.00975058

Gnomad4 AMR

AF:

0.00320

AC:

0.00320387

AN:

0.00320387

Gnomad4 ASJ

AF:

0.000576

AC:

0.000576369

AN:

0.000576369

Gnomad4 EAS

AF:

0.000773

AC:

0.000773096

AN:

0.000773096

Gnomad4 SAS

AF:

0.00353

AC:

0.00352551

AN:

0.00352551

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.00163

AC:

0.0016324

AN:

0.0016324

Gnomad4 OTH

AF:

0.00662

AC:

0.00662252

AN:

0.00662252

Heterozygous variant carriers

114

143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00327

Hom.:

Bravo

AF:

0.00440

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.00257

EpiControl

AF:

0.00303

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ITPR3: BS2 -

Apr 10, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=100/0

polymorphism

Splicing

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