6-33640439-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002224.4(ITPR3):c.90-45G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,580,972 control chromosomes in the GnomAD database, including 12,374 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (840 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11534 hom.)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.732

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 6-33640439-G-T is Benign according to our data. Variant chr6-33640439-G-T is described in ClinVar as [Benign]. Clinvar id is 1293544.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITPR3	NM_002224.4	c.90-45G>T		intron_variant		ENST00000605930.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPR3	ENST00000605930.3	c.90-45G>T		intron_variant		1	NM_002224.4	P1
ITPR3	ENST00000374316.9	c.90-45G>T		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15508 AN: 152168 Hom.: 838 Cov.: 32

Gnomad AFR AF: 0.0917

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0602

Gnomad EAS AF: 0.0212

Gnomad SAS AF: 0.0839

Gnomad FIN AF: 0.0812

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.0856

GnomAD3 exomes AF: 0.101 AC: 23852 AN: 235190 Hom.: 1368 AF XY: 0.0999 AC XY: 12718 AN XY: 127294

Gnomad AFR exome AF: 0.0878

Gnomad AMR exome AF: 0.134

Gnomad ASJ exome AF: 0.0593

Gnomad EAS exome AF: 0.0154

Gnomad SAS exome AF: 0.0852

Gnomad FIN exome AF: 0.0852

Gnomad NFE exome AF: 0.119

Gnomad OTH exome AF: 0.100

GnomAD4 exome AF: 0.122 AC: 174935 AN: 1428686 Hom.: 11534 Cov.: 26 AF XY: 0.121 AC XY: 86028 AN XY: 711360

Gnomad4 AFR exome AF: 0.0797

Gnomad4 AMR exome AF: 0.126

Gnomad4 ASJ exome AF: 0.0630

Gnomad4 EAS exome AF: 0.0330

Gnomad4 SAS exome AF: 0.0873

Gnomad4 FIN exome AF: 0.0911

Gnomad4 NFE exome AF: 0.133

Gnomad4 OTH exome AF: 0.114

GnomAD4 genome AF: 0.102 AC: 15518 AN: 152286 Hom.: 840 Cov.: 32 AF XY: 0.0986 AC XY: 7339 AN XY: 74460

Gnomad4 AFR AF: 0.0916

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.0602

Gnomad4 EAS AF: 0.0212

Gnomad4 SAS AF: 0.0836

Gnomad4 FIN AF: 0.0812

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.0848

Alfa AF: 0.107 Hom.: 305

Bravo AF: 0.103

Asia WGS AF: 0.0690 AC: 241 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.2
Dann	Benign	0.74

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

Other links and lift over

dbSNP: rs41271247; hg19: chr6-33608216;