Variant 1-226735756-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002221.4(ITPKB):c.1703C>T(p.Ala568Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,444,812 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ITPKB
NM_002221.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.18

Variant links:

Genes affected

ITPKB (HGNC:6179): (inositol-trisphosphate 3-kinase B) The protein encoded by this protein regulates inositol phosphate metabolism by phosphorylation of second messenger inositol 1,4,5-trisphosphate to Ins(1,3,4,5)P4. The activity of this encoded protein is responsible for regulating the levels of a large number of inositol polyphosphates that are important in cellular signaling. Both calcium/calmodulin and protein phosphorylation mechanisms control its activity. [provided by RefSeq, Jul 2008]

ITPKB links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ITPKB	NM_002221.4 linkuse as main transcript	c.1703C>T	p.Ala568Val	missense_variant	2/8	ENST00000429204.6
ITPKB	NM_001388404.1 linkuse as main transcript	c.1703C>T	p.Ala568Val	missense_variant	2/3
ITPKB	XM_017001211.3 linkuse as main transcript	c.1703C>T	p.Ala568Val	missense_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPKB	ENST00000429204.6 linkuse as main transcript	c.1703C>T	p.Ala568Val	missense_variant	2/8	5	NM_002221.4	P1	P27987-1
ITPKB	ENST00000272117.8 linkuse as main transcript	c.1703C>T	p.Ala568Val	missense_variant	2/8	1		P1	P27987-1
ITPKB	ENST00000366784.1 linkuse as main transcript	c.1703C>T	p.Ala568Val	missense_variant	2/3	1			P27987-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000408

AC:

AN:

245368

Hom.:

AF XY:

0.00

AC XY:

AN XY:

132544

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000902

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1444812

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715646

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000182

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 27, 2022

The c.1703C>T (p.A568V) alteration is located in exon 2 (coding exon 1) of the ITPKB gene. This alteration results from a C to T substitution at nucleotide position 1703, causing the alanine (A) at amino acid position 568 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Uncertain

0.059

BayesDel_noAF

Benign

-0.15

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.24

T;T;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.99

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.63

D;D;D

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.9

L;L;L

MutationTaster

Benign

0.95

D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.4

N;N;D

REVEL

Benign

0.18

Sift

Uncertain

0.0010

D;D;D

Sift4G

Benign

0.15

T;T;D

Polyphen

1.0

D;D;.

Vest4

0.76

MutPred

0.22

Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);

MVP

0.41

MPC

0.77

ClinPred

0.75

GERP RS

5.5

Varity_R

0.16

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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