chr19-40740473-G-C

Variant names:

• chr19-40740473-G-C
• rs2290692
• NM_025194.3:c.*913G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025194.3(ITPKC):​c.*913G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 203,946 control chromosomes in the GnomAD database, including 23,132 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 0.46 (16846 hom., cov: 33)
  • Exomes 𝑓: 0.48 (6286 hom.)
• Consequence: ITPKC NM_025194.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.95
• Publications: 22 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025194.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPKC	NM_025194.3	MANE Select	c.*913G>C		3_prime_UTR	Exon 7 of 7	NP_079470.1
	ITPKC	NM_001411098.1		c.*913G>C		3_prime_UTR	Exon 6 of 6	NP_001398027.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPKC	ENST00000263370.3	TSL:1 MANE Select	c.*913G>C		3_prime_UTR	Exon 7 of 7	ENSP00000263370.1
	ITPKC	ENST00000699490.1		c.*405G>C		3_prime_UTR	Exon 8 of 8	ENSP00000514401.1
	ITPKC	ENST00000699489.1		c.*913G>C		3_prime_UTR	Exon 6 of 6	ENSP00000514400.1

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69682 AN: 151994 Hom.: 16829 Cov.: 33

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.475

GnomAD4 exome AF: 0.484 AC: 25107 AN: 51834 Hom.: 6286 Cov.: 0 AF XY: 0.486 AC XY: 13090 AN XY: 26924

African (AFR) AF: 0.253 AC: 377 AN: 1488

American (AMR) AF: 0.621 AC: 749 AN: 1206

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 681 AN: 1778

East Asian (EAS) AF: 0.582 AC: 2635 AN: 4524

South Asian (SAS) AF: 0.579 AC: 270 AN: 466

European-Finnish (FIN) AF: 0.514 AC: 3055 AN: 5942

Middle Eastern (MID) AF: 0.430 AC: 99 AN: 230

European-Non Finnish (NFE) AF: 0.478 AC: 15820 AN: 33100

Other (OTH) AF: 0.458 AC: 1421 AN: 3100

GnomAD4 genome AF: 0.458 AC: 69721 AN: 152112 Hom.: 16846 Cov.: 33 AF XY: 0.463 AC XY: 34470 AN XY: 74376

African (AFR) AF: 0.309 AC: 12812 AN: 41522

American (AMR) AF: 0.564 AC: 8623 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1481 AN: 3472

East Asian (EAS) AF: 0.546 AC: 2815 AN: 5158

South Asian (SAS) AF: 0.582 AC: 2808 AN: 4822

European-Finnish (FIN) AF: 0.539 AC: 5698 AN: 10574

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33836 AN: 67970

Other (OTH) AF: 0.477 AC: 1006 AN: 2110

Alfa AF: 0.337 Hom.: 960

Bravo AF: 0.453

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.017
DANN	Benign	0.37
PhyloP100		-2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2290692; hg19: chr19-41246378;