Variant 19-40718299-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_025194.3(ITPKC):c.1155+9G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,503,416 control chromosomes in the GnomAD database, including 12,452 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.10 ( 1034 hom., cov: 32)

Exomes 𝑓: 0.13 ( 11418 hom. )

Consequence

ITPKC
NM_025194.3 intron

Scores

Clinical Significance

Conflicting classifications of pathogenicity no assertion criteria provided U:1B:1

Conservation

PhyloP100: 0.915

Variant links:

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]

ITPKC links:

COQ8B (HGNC:19041): (coenzyme Q8B) This gene encodes a protein with two copies of a domain found in protein kinases. The encoded protein has a complete protein kinase catalytic domain, and a truncated domain that contains only the active and binding sites of the protein kinase domain, however, it is not known whether the protein has any kinase activity. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

COQ8B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPKC	NM_025194.3 link	c.1155+9G>C		intron_variant		ENST00000263370.3	NP_079470.1	Q96DU7A0A024R0N8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPKC	ENST00000263370.3 link	c.1155+9G>C		intron_variant		1	NM_025194.3	ENSP00000263370.1		Q96DU7

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15556

AN:

152030

Hom.:

1032

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0323

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.114

Gnomad EAS

AF:

0.0745

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.129

Gnomad OTH

AF:

0.101

GnomAD3 exomes

AF:

0.121

AC:

20177

AN:

167104

Hom.:

1372

AF XY:

0.122

AC XY:

10904

AN XY:

89192

show subpopulations

Gnomad AFR exome

AF:

0.0300

Gnomad AMR exome

AF:

0.192

Gnomad ASJ exome

AF:

0.107

Gnomad EAS exome

AF:

0.0675

Gnomad SAS exome

AF:

0.125

Gnomad FIN exome

AF:

0.138

Gnomad NFE exome

AF:

0.126

Gnomad OTH exome

AF:

0.123

GnomAD4 exome

AF:

0.128

AC:

172968

AN:

1351266

Hom.:

11418

Cov.:

AF XY:

0.128

AC XY:

84775

AN XY:

661624

show subpopulations

Gnomad4 AFR exome

AF:

0.0275

Gnomad4 AMR exome

AF:

0.186

Gnomad4 ASJ exome

AF:

0.104

Gnomad4 EAS exome

AF:

0.120

Gnomad4 SAS exome

AF:

0.125

Gnomad4 FIN exome

AF:

0.145

Gnomad4 NFE exome

AF:

0.130

Gnomad4 OTH exome

AF:

0.123

GnomAD4 genome

AF:

0.102

AC:

15565

AN:

152150

Hom.:

1034

Cov.:

AF XY:

0.104

AC XY:

7718

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0322

Gnomad4 AMR

AF:

0.144

Gnomad4 ASJ

AF:

0.114

Gnomad4 EAS

AF:

0.0744

Gnomad4 SAS

AF:

0.118

Gnomad4 FIN

AF:

0.151

Gnomad4 NFE

AF:

0.129

Gnomad4 OTH

AF:

0.0993

Alfa

AF:

0.123

Hom.:

675

Bravo

AF:

0.0977

Asia WGS

AF:

0.0860

AC:

299

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Reclassified - variant of unknown significance

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Mar 15, 2010

- -

ITPKC-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 15, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.76

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over