6-33655732-T-C

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.161-34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.047 in 1,613,086 control chromosomes in the GnomAD database, including 2,063 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.050 (222 hom., cov: 32)
  • Exomes 𝑓: 0.047 (1841 hom.)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.323

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=-0.93).
• BP6: Variant 6-33655732-T-C is Benign according to our data. Variant chr6-33655732-T-C is described in ClinVar as [Benign]. Clinvar id is 1270368.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.068 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITPR3	NM_002224.4	c.161-34T>C		intron_variant		ENST00000605930.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPR3	ENST00000605930.3	c.161-34T>C		intron_variant		1	NM_002224.4	P1
ITPR3	ENST00000374316.9	c.161-34T>C		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.0497 AC: 7550 AN: 152034 Hom.: 220 Cov.: 32

Gnomad AFR AF: 0.0698

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0383

Gnomad ASJ AF: 0.0439

Gnomad EAS AF: 0.00828

Gnomad SAS AF: 0.0141

Gnomad FIN AF: 0.0199

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0507

Gnomad OTH AF: 0.0511

GnomAD3 exomes AF: 0.0371 AC: 9257 AN: 249548 Hom.: 247 AF XY: 0.0356 AC XY: 4806 AN XY: 135014

Gnomad AFR exome AF: 0.0683

Gnomad AMR exome AF: 0.0249

Gnomad ASJ exome AF: 0.0434

Gnomad EAS exome AF: 0.0113

Gnomad SAS exome AF: 0.0145

Gnomad FIN exome AF: 0.0217

Gnomad NFE exome AF: 0.0489

Gnomad OTH exome AF: 0.0405

GnomAD4 exome AF: 0.0468 AC: 68311 AN: 1460934 Hom.: 1841 Cov.: 31 AF XY: 0.0453 AC XY: 32895 AN XY: 726688

Gnomad4 AFR exome AF: 0.0660

Gnomad4 AMR exome AF: 0.0283

Gnomad4 ASJ exome AF: 0.0411

Gnomad4 EAS exome AF: 0.00695

Gnomad4 SAS exome AF: 0.0145

Gnomad4 FIN exome AF: 0.0212

Gnomad4 NFE exome AF: 0.0524

Gnomad4 OTH exome AF: 0.0434

GnomAD4 genome AF: 0.0498 AC: 7573 AN: 152152 Hom.: 222 Cov.: 32 AF XY: 0.0478 AC XY: 3554 AN XY: 74402

Gnomad4 AFR AF: 0.0702

Gnomad4 AMR AF: 0.0383

Gnomad4 ASJ AF: 0.0439

Gnomad4 EAS AF: 0.00830

Gnomad4 SAS AF: 0.0139

Gnomad4 FIN AF: 0.0199

Gnomad4 NFE AF: 0.0507

Gnomad4 OTH AF: 0.0506

Alfa AF: 0.0489 Hom.: 33

Bravo AF: 0.0527

Asia WGS AF: 0.0140 AC: 48 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	-0.93
Cadd	Benign	8.2
Dann	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs78064999; hg19: chr6-33623509;