chr19-40718409-G-A

Position:

• chr19-40718409-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025194.3(ITPKC):​c.1155+119G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 1,309,614 control chromosomes in the GnomAD database, including 225,359 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 0.62 (29232 hom., cov: 31)
  • Exomes 𝑓: 0.58 (196127 hom.)
• Consequence: ITPKC NM_025194.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.381

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]

COQ8B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPKC	NM_025194.3	c.1155+119G>A		intron_variant		ENST00000263370.3	NP_079470.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPKC	ENST00000263370.3	c.1155+119G>A		intron_variant		1	NM_025194.3	ENSP00000263370.1

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93565 AN: 151800 Hom.: 29192 Cov.: 31

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.588

GnomAD4 exome AF: 0.579 AC: 670112 AN: 1157696 Hom.: 196127 AF XY: 0.578 AC XY: 326145 AN XY: 563934

Gnomad4 AFR exome AF: 0.680

Gnomad4 AMR exome AF: 0.679

Gnomad4 ASJ exome AF: 0.507

Gnomad4 EAS exome AF: 0.776

Gnomad4 SAS exome AF: 0.569

Gnomad4 FIN exome AF: 0.665

Gnomad4 NFE exome AF: 0.565

Gnomad4 OTH exome AF: 0.590

GnomAD4 genome AF: 0.617 AC: 93661 AN: 151918 Hom.: 29232 Cov.: 31 AF XY: 0.620 AC XY: 45995 AN XY: 74232

Gnomad4 AFR AF: 0.679

Gnomad4 AMR AF: 0.645

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.724

Gnomad4 SAS AF: 0.574

Gnomad4 FIN AF: 0.674

Gnomad4 NFE AF: 0.564

Gnomad4 OTH AF: 0.591

Alfa AF: 0.570 Hom.: 31050

Bravo AF: 0.619

Asia WGS AF: 0.658 AC: 2288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.2
DANN	Benign	0.74

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: rs2561530; hg19: chr19-41224314;