rs10420685

chr19-40729215-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_025194.3(ITPKC):c.1269A>G(p.Ala423=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0631 in 1,613,686 control chromosomes in the GnomAD database, including 4,806 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 0.096 (1035 hom., cov: 32)
  • Exomes 𝑓: 0.060 (3771 hom.)
• Consequence: ITPKC NM_025194.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.88

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP7: Synonymous conserved (PhyloP=-2.88 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITPKC	NM_025194.3	c.1269A>G	p.Ala423=	synonymous_variant	3/7	ENST00000263370.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPKC	ENST00000263370.3	c.1269A>G	p.Ala423=	synonymous_variant	3/7	1	NM_025194.3	P1
ITPKC	ENST00000699490.1	c.1269A>G	p.Ala423=	synonymous_variant	3/8			P1
ITPKC	ENST00000699489.1	c.1269A>G	p.Ala423=	synonymous_variant	3/6
ITPKC	ENST00000699488.1	c.1156-3945A>G		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0962 AC: 14621 AN: 152040 Hom.: 1029 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.0615

Gnomad AMR AF: 0.0488

Gnomad ASJ AF: 0.0617

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.0499

Gnomad FIN AF: 0.0795

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0479

Gnomad OTH AF: 0.0761

GnomAD3 exomes AF: 0.0725 AC: 18209 AN: 251242 Hom.: 1136 AF XY: 0.0695 AC XY: 9441 AN XY: 135826

Gnomad AFR exome AF: 0.193

Gnomad AMR exome AF: 0.0293

Gnomad ASJ exome AF: 0.0608

Gnomad EAS exome AF: 0.228

Gnomad SAS exome AF: 0.0444

Gnomad FIN exome AF: 0.0871

Gnomad NFE exome AF: 0.0500

Gnomad OTH exome AF: 0.0548

GnomAD4 exome AF: 0.0597 AC: 87191 AN: 1461528 Hom.: 3771 Cov.: 32 AF XY: 0.0587 AC XY: 42696 AN XY: 727100

Gnomad4 AFR exome AF: 0.204

Gnomad4 AMR exome AF: 0.0309

Gnomad4 ASJ exome AF: 0.0628

Gnomad4 EAS exome AF: 0.236

Gnomad4 SAS exome AF: 0.0445

Gnomad4 FIN exome AF: 0.0866

Gnomad4 NFE exome AF: 0.0494

Gnomad4 OTH exome AF: 0.0705

GnomAD4 genome AF: 0.0963 AC: 14651 AN: 152158 Hom.: 1035 Cov.: 32 AF XY: 0.0965 AC XY: 7181 AN XY: 74392

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.0488

Gnomad4 ASJ AF: 0.0617

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.0491

Gnomad4 FIN AF: 0.0795

Gnomad4 NFE AF: 0.0479

Gnomad4 OTH AF: 0.0763

Alfa AF: 0.0631 Hom.: 443

Bravo AF: 0.101

Asia WGS AF: 0.130 AC: 451 AN: 3478

EpiCase AF: 0.0483

EpiControl AF: 0.0475

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	2.9
Dann	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10420685; hg19: chr19-41235120; COSMIC: COSV54574453; COSMIC: COSV54574453;