rs2290692

Positions:

• chr19-40740473-G-A
• chr19-40740473-G-C
• chr19-40740473-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_025194.3(ITPKC):​c.*913G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00478 in 204,292 control chromosomes in the GnomAD database, including 4 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 0.0047 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0051 (1 hom.)
• Consequence: ITPKC NM_025194.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.95

Genes affected

ITPKC (HGNC:14897): (inositol-trisphosphate 3-kinase C) This gene encodes a member of the inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] 3-kinase family of enzymes that catalyze the phosphorylation of inositol 1,4,5-trisphosphate to 1,3,4,5-tetrakisphosphate. The encoded protein is localized to the nucleus and cytoplasm and has both nuclear import and nuclear export activity. Single nucleotide polymorphisms in this gene are associated with Kawasaki disease.[provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPKC	NM_025194.3	c.*913G>A		3_prime_UTR_variant	7/7	ENST00000263370.3	NP_079470.1
ITPKC	NM_001411098.1	c.*913G>A		3_prime_UTR_variant	6/6		NP_001398027.1
ITPKC	XM_047439466.1	c.*543G>A		3_prime_UTR_variant	8/8		XP_047295422.1
ITPKC	XM_047439468.1	c.*1622G>A		3_prime_UTR_variant	7/7		XP_047295424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPKC	ENST00000263370.3	c.*913G>A		3_prime_UTR_variant	7/7	1	NM_025194.3	ENSP00000263370.1

Frequencies

GnomAD3 genomes AF: 0.00468 AC: 711 AN: 152044 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000628

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00668

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00621

Gnomad FIN AF: 0.00643

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00681

Gnomad OTH AF: 0.00526

GnomAD4 exome AF: 0.00512 AC: 267 AN: 52130 Hom.: 1 Cov.: 0 AF XY: 0.00451 AC XY: 122 AN XY: 27062

Gnomad4 AFR exome AF: 0.000669

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00112

Gnomad4 EAS exome AF: 0.000220

Gnomad4 SAS exome AF: 0.00426

Gnomad4 FIN exome AF: 0.00552

Gnomad4 NFE exome AF: 0.00655

Gnomad4 OTH exome AF: 0.00289

GnomAD4 genome AF: 0.00467 AC: 710 AN: 152162 Hom.: 3 Cov.: 33 AF XY: 0.00485 AC XY: 361 AN XY: 74400

Gnomad4 AFR AF: 0.000626

Gnomad4 AMR AF: 0.00667

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00601

Gnomad4 FIN AF: 0.00643

Gnomad4 NFE AF: 0.00681

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00821 Hom.: 960

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.034
DANN	Benign	0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2290692; hg19: chr19-41246378;