6-33657823-GT-G

Position:

• chr6-33657823-GT-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002224.4(ITPR3):​c.283-108del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 815,184 control chromosomes in the GnomAD database, including 55,051 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.36 (10353 hom., cov: 0)
  • Exomes 𝑓: 0.35 (44698 hom.)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.12

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 6-33657823-GT-G is Benign according to our data. Variant chr6-33657823-GT-G is described in ClinVar as [Benign]. Clinvar id is 1247934.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITPR3	NM_002224.4	c.283-108del		intron_variant		ENST00000605930.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPR3	ENST00000605930.3	c.283-108del		intron_variant		1	NM_002224.4	P1
ITPR3	ENST00000374316.9	c.283-108del		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 54990 AN: 151416 Hom.: 10336 Cov.: 0

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.332

GnomAD4 exome AF: 0.350 AC: 232509 AN: 663650 Hom.: 44698 AF XY: 0.358 AC XY: 125104 AN XY: 349884

Gnomad4 AFR exome AF: 0.451

Gnomad4 AMR exome AF: 0.284

Gnomad4 ASJ exome AF: 0.276

Gnomad4 EAS exome AF: 0.465

Gnomad4 SAS exome AF: 0.522

Gnomad4 FIN exome AF: 0.376

Gnomad4 NFE exome AF: 0.318

Gnomad4 OTH exome AF: 0.351

GnomAD4 genome AF: 0.363 AC: 55037 AN: 151534 Hom.: 10353 Cov.: 0 AF XY: 0.367 AC XY: 27169 AN XY: 74016

Gnomad4 AFR AF: 0.437

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.522

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.337

Alfa AF: 0.167 Hom.: 305

Bravo AF: 0.359

Asia WGS AF: 0.541 AC: 1879 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs3831079; hg19: chr6-33625600;