Variant 14-92941617-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_014216.6(ITPK1):c.1189C>T(p.Pro397Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 1,538,016 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

ITPK1
NM_014216.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.86

Variant links:

Genes affected

ITPK1 (HGNC:6177): (inositol-tetrakisphosphate 1-kinase) This gene encodes an enzyme that belongs to the inositol 1,3,4-trisphosphate 5/6-kinase family. This enzyme regulates the synthesis of inositol tetraphosphate, and downstream products, inositol pentakisphosphate and inositol hexakisphosphate. Inositol metabolism plays a role in the development of the neural tube. Disruptions in this gene are thought to be associated with neural tube defects. A pseudogene of this gene has been identified on chromosome X. [provided by RefSeq, Jul 2016]

ITPK1 links:

Genome browser will be placed here

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	Protein	UniProt
ITPK1	NM_014216.6 linkuse as main transcript	c.1189C>T	p.Pro397Ser	missense_variant	11/11	ENST00000267615.11	NP_055031.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPK1	ENST00000267615.11 linkuse as main transcript	c.1189C>T	p.Pro397Ser	missense_variant	11/11	1	NM_014216.6	ENSP00000267615	P1	Q13572-1
ITPK1	ENST00000556603.6 linkuse as main transcript	c.1189C>T	p.Pro397Ser	missense_variant	11/11	1		ENSP00000451091	P1	Q13572-1
ITPK1	ENST00000555495.5 linkuse as main transcript	c.832C>T	p.Pro278Ser	missense_variant	9/9	1		ENSP00000451893
ITPK1	ENST00000354313.7 linkuse as main transcript	c.902-3091C>T		intron_variant		1		ENSP00000346272		Q13572-2

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000830

AC:

AN:

132508

Hom.:

AF XY:

0.0000553

AC XY:

AN XY:

72384

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:

0.0000874

Gnomad NFE exome

AF:

0.000203

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000212

AC:

294

AN:

1385762

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

138

AN XY:

683696

show subpopulations

Gnomad4 AFR exome

AF:

0.000161

Gnomad4 AMR exome

AF:

0.0000296

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000127

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000259

Gnomad4 OTH exome

AF:

0.000139

GnomAD4 genome

AF:

0.000118

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000268

Hom.:

Bravo

AF:

0.000125

ExAC

AF:

0.0000809

AC:

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

Feb 22, 2023

The c.1189C>T (p.P397S) alteration is located in exon 11 (coding exon 10) of the ITPK1 gene. This alteration results from a C to T substitution at nucleotide position 1189, causing the proline (P) at amino acid position 397 to be replaced by a serine (S). 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

0.12

BayesDel_addAF

Benign

-0.032

BayesDel_noAF

Uncertain

0.020

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;T;.

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.21

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.050

MetaRNN

Uncertain

0.44

T;T;T

MetaSVM

Benign

-0.68

MutationAssessor

Benign

1.0

L;L;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.0

N;N;N

REVEL

Benign

0.27

Sift

Uncertain

0.010

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.82

P;P;.

Vest4

0.70

MVP

0.17

MPC

1.0

ClinPred

0.24

GERP RS

3.9

Varity_R

0.16

gMVP

0.41

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