6-33680451-C-T

Variant names:

• chr6-33680451-C-T
• rs2229638
• NM_002224.4:c.4347C>T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_002224.4(ITPR3):​c.4347C>T​(p.Ala1449Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 1,613,004 control chromosomes in the GnomAD database, including 651,893 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.90 (61580 hom., cov: 35)
  • Exomes 𝑓: 0.90 (590313 hom.)
• Consequence: ITPR3 NM_002224.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=0.058 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR3	NM_002224.4	c.4347C>T	p.Ala1449Ala	synonymous_variant	Exon 32 of 58	ENST00000605930.3	NP_002215.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPR3	ENST00000605930.3	c.4347C>T	p.Ala1449Ala	synonymous_variant	Exon 32 of 58	1	NM_002224.4	ENSP00000475177.1
ITPR3	ENST00000374316.9	c.4347C>T	p.Ala1449Ala	synonymous_variant	Exon 33 of 59	5		ENSP00000363435.4

Frequencies

GnomAD3 genomes AF: 0.899 AC: 136757 AN: 152188 Hom.: 61540 Cov.: 35

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.906

Gnomad AMR AF: 0.930

Gnomad ASJ AF: 0.958

Gnomad EAS AF: 0.989

Gnomad SAS AF: 0.922

Gnomad FIN AF: 0.942

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.899

Gnomad OTH AF: 0.903

GnomAD3 exomes AF: 0.919 AC: 229942 AN: 250160 Hom.: 105898 AF XY: 0.919 AC XY: 124391 AN XY: 135292

Gnomad AFR exome AF: 0.851

Gnomad AMR exome AF: 0.949

Gnomad ASJ exome AF: 0.960

Gnomad EAS exome AF: 0.993

Gnomad SAS exome AF: 0.918

Gnomad FIN exome AF: 0.937

Gnomad NFE exome AF: 0.902

Gnomad OTH exome AF: 0.911

GnomAD4 exome AF: 0.899 AC: 1312481 AN: 1460698 Hom.: 590313 Cov.: 80 AF XY: 0.900 AC XY: 653683 AN XY: 726708

Gnomad4 AFR exome AF: 0.856

Gnomad4 AMR exome AF: 0.946

Gnomad4 ASJ exome AF: 0.958

Gnomad4 EAS exome AF: 0.996

Gnomad4 SAS exome AF: 0.915

Gnomad4 FIN exome AF: 0.933

Gnomad4 NFE exome AF: 0.890

Gnomad4 OTH exome AF: 0.900

GnomAD4 genome AF: 0.899 AC: 136854 AN: 152306 Hom.: 61580 Cov.: 35 AF XY: 0.904 AC XY: 67336 AN XY: 74458

Gnomad4 AFR AF: 0.855

Gnomad4 AMR AF: 0.930

Gnomad4 ASJ AF: 0.958

Gnomad4 EAS AF: 0.989

Gnomad4 SAS AF: 0.921

Gnomad4 FIN AF: 0.942

Gnomad4 NFE AF: 0.899

Gnomad4 OTH AF: 0.904

Alfa AF: 0.903 Hom.: 98947

Bravo AF: 0.896

Asia WGS AF: 0.944 AC: 3283 AN: 3478

EpiCase AF: 0.904

EpiControl AF: 0.903

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	1.2
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: rs2229638; hg19: chr6-33648228; COSMIC: COSV65406724;