rs201162163

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002221.4(ITPKB):c.1273G>A(p.Glu425Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000122 in 1,392,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ITPKB
NM_002221.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.879

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

ITPKB deficiency
Inheritance: AR Classification: LIMITED Submitted by: ClinGen
Tourette syndrome
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ITPKB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.041062832).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPKB	NM_002221.4 link	c.1273G>A	p.Glu425Lys	missense_variant	Exon 2 of 8	ENST00000429204.6	NP_002212.3	P27987-1B2R9J0
ITPKB	NM_001388404.1 link	c.1273G>A	p.Glu425Lys	missense_variant	Exon 2 of 3		NP_001375333.1
ITPKB	XM_017001211.3 link	c.1273G>A	p.Glu425Lys	missense_variant	Exon 2 of 3		XP_016856700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ITPKB	ENST00000429204.6 link	c.1273G>A	p.Glu425Lys	missense_variant	Exon 2 of 8	5	NM_002221.4	ENSP00000411152.1	P27987-1
ITPKB	ENST00000272117.8 link	c.1273G>A	p.Glu425Lys	missense_variant	Exon 2 of 8	1		ENSP00000272117.3	P27987-1
ITPKB	ENST00000366784.1 link	c.1273G>A	p.Glu425Lys	missense_variant	Exon 2 of 3	1		ENSP00000355748.1	P27987-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000526

AC:

AN:

190008

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000122

AC:

AN:

1392324

Hom.:

Cov.:

AF XY:

0.0000160

AC XY:

AN XY:

685456

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31266

American (AMR)

AF:

0.00

AC:

AN:

34954

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21178

East Asian (EAS)

AF:

0.00

AC:

AN:

39222

South Asian (SAS)

AF:

0.000215

AC:

AN:

74302

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49118

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5392

European-Non Finnish (NFE)

AF:

9.26e-7

AC:

AN:

1079624

Other (OTH)

AF:

0.00

AC:

AN:

57268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000250

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 06, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1273G>A (p.E425K) alteration is located in exon 2 (coding exon 1) of the ITPKB gene. This alteration results from a G to A substitution at nucleotide position 1273, causing the glutamic acid (E) at amino acid position 425 to be replaced by a lysine (K). 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

Benign

0.091

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.78

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.034

T;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.69

.;T;T

M_CAP

Benign

0.0057

MetaRNN

Benign

0.041

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.63

N;N;N

PhyloP100

0.88

PrimateAI

Benign

0.43

PROVEAN

Benign

0.23

N;N;N

REVEL

Benign

0.013

Sift

Benign

0.74

T;T;T

Sift4G

Benign

0.90

T;T;T

Polyphen

0.0010

B;B;.

Vest4

0.074

MutPred

0.29

Gain of MoRF binding (P = 0.0026);Gain of MoRF binding (P = 0.0026);Gain of MoRF binding (P = 0.0026);

MVP

0.23

MPC

0.22

ClinPred

0.028

GERP RS

2.6

Varity_R

0.035

gMVP

0.21

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over