6-33689469-C-T

Position:

• chr6-33689469-C-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.6867+59C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 1,573,584 control chromosomes in the GnomAD database, including 180,436 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (15253 hom., cov: 33)
  • Exomes 𝑓: 0.47 (165183 hom.)
• Consequence: ITPR3 NM_002224.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.238

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=-0.81).
• BP6: Variant 6-33689469-C-T is Benign according to our data. Variant chr6-33689469-C-T is described in ClinVar as [Benign]. Clinvar id is 1259455.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITPR3	NM_002224.4	c.6867+59C>T		intron_variant		ENST00000605930.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPR3	ENST00000605930.3	c.6867+59C>T		intron_variant		1	NM_002224.4	P1
ITPR3	ENST00000374316.9	c.6867+59C>T		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62305 AN: 152014 Hom.: 15250 Cov.: 33

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.386

GnomAD4 exome AF: 0.469 AC: 667169 AN: 1421452 Hom.: 165183 AF XY: 0.478 AC XY: 337150 AN XY: 705778

Gnomad4 AFR exome AF: 0.157

Gnomad4 AMR exome AF: 0.614

Gnomad4 ASJ exome AF: 0.461

Gnomad4 EAS exome AF: 0.819

Gnomad4 SAS exome AF: 0.701

Gnomad4 FIN exome AF: 0.587

Gnomad4 NFE exome AF: 0.439

Gnomad4 OTH exome AF: 0.463

GnomAD4 genome AF: 0.410 AC: 62316 AN: 152132 Hom.: 15253 Cov.: 33 AF XY: 0.429 AC XY: 31885 AN XY: 74380

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.853

Gnomad4 SAS AF: 0.720

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.386

Alfa AF: 0.292 Hom.: 860

Bravo AF: 0.388

Asia WGS AF: 0.695 AC: 2417 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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.2
DANN	Benign	0.55

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: rs3818521; hg19: chr6-33657246; COSMIC: COSV65409484; COSMIC: COSV65409484;