6-33621255-G-C

Position:

• chr6-33621255-G-C

Variant summary

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

The ENST00000374316.9(ITPR3):​c.-348G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.928 in 144,042 control chromosomes in the GnomAD database, including 62,213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.93 (61069 hom., cov: 22)
  • Exomes 𝑓: 0.96 (1144 hom.)
• Consequence: ITPR3 ENST00000374316.9 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.899

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=-0.76).
• BP6: Variant 6-33621255-G-C is Benign according to our data. Variant chr6-33621255-G-C is described in ClinVar as [Benign]. Clinvar id is 1276370.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPR3	ENST00000374316.9	c.-348G>C		5_prime_UTR_variant	2/59	5		P1

Frequencies

GnomAD3 genomes AF: 0.928 AC: 131240 AN: 141464 Hom.: 61028 Cov.: 22

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.939

Gnomad AMR AF: 0.955

Gnomad ASJ AF: 0.954

Gnomad EAS AF: 0.980

Gnomad SAS AF: 0.971

Gnomad FIN AF: 0.961

Gnomad MID AF: 0.895

Gnomad NFE AF: 0.953

Gnomad OTH AF: 0.916

GnomAD4 exome AF: 0.959 AC: 2380 AN: 2482 Hom.: 1144 Cov.: 0 AF XY: 0.963 AC XY: 1244 AN XY: 1292

Gnomad4 AFR exome AF: 0.815

Gnomad4 AMR exome AF: 0.883

Gnomad4 ASJ exome AF: 0.938

Gnomad4 EAS exome AF: 0.991

Gnomad4 SAS exome AF: 0.984

Gnomad4 FIN exome AF: 0.967

Gnomad4 NFE exome AF: 0.968

Gnomad4 OTH exome AF: 0.974

GnomAD4 genome AF: 0.928 AC: 131328 AN: 141560 Hom.: 61069 Cov.: 22 AF XY: 0.930 AC XY: 64306 AN XY: 69148

Gnomad4 AFR AF: 0.855

Gnomad4 AMR AF: 0.955

Gnomad4 ASJ AF: 0.954

Gnomad4 EAS AF: 0.980

Gnomad4 SAS AF: 0.970

Gnomad4 FIN AF: 0.961

Gnomad4 NFE AF: 0.953

Gnomad4 OTH AF: 0.917

Alfa AF: 0.778 Hom.: 389

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	-0.76
CADD	Benign	11
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6910386; hg19: chr6-33589032; COSMIC: COSV65414820; COSMIC: COSV65414820;