Variant chr10-22550699-T-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_005028.5(PIP4K2A):c.752A>G(p.Asn251Ser) variant causes a missense change. The variant allele was found at a frequency of 0.296 in 1,598,884 control chromosomes in the GnomAD database, including 74,535 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.24 ( 5183 hom., cov: 32)

Exomes 𝑓: 0.30 ( 69352 hom. )

Consequence

PIP4K2A
NM_005028.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.89

Variant links:

Genes affected

PIP4K2A (HGNC:8997): (phosphatidylinositol-5-phosphate 4-kinase type 2 alpha) Phosphatidylinositol-5,4-bisphosphate, the precursor to second messengers of the phosphoinositide signal transduction pathways, is thought to be involved in the regulation of secretion, cell proliferation, differentiation, and motility. The protein encoded by this gene is one of a family of enzymes capable of catalyzing the phosphorylation of phosphatidylinositol-5-phosphate on the fourth hydroxyl of the myo-inositol ring to form phosphatidylinositol-5,4-bisphosphate. The amino acid sequence of this enzyme does not show homology to other kinases, but the recombinant protein does exhibit kinase activity. This gene is a member of the phosphatidylinositol-5-phosphate 4-kinase family. [provided by RefSeq, Jul 2008]

PIP4K2A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031907558).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIP4K2A	NM_005028.5 linkuse as main transcript	c.752A>G	p.Asn251Ser	missense_variant	7/10	ENST00000376573.9	NP_005019.2	P48426-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PIP4K2A	ENST00000376573.9 linkuse as main transcript	c.752A>G	p.Asn251Ser	missense_variant	7/10	1	NM_005028.5	ENSP00000365757.4	P48426-1
PIP4K2A	ENST00000545335.5 linkuse as main transcript	c.575A>G	p.Asn192Ser	missense_variant	7/10	2		ENSP00000442098.1	P48426-2
PIP4K2A	ENST00000323883.11 linkuse as main transcript	c.332A>G	p.Asn111Ser	missense_variant	5/8	2		ENSP00000326294.7	H7BXS3
PIP4K2A	ENST00000604912.1 linkuse as main transcript	c.290A>G	p.Asn97Ser	missense_variant	4/5	2		ENSP00000473858.1	S4R320

Frequencies

GnomAD3 genomes

AF:

0.237

AC:

36103

AN:

152040

Hom.:

5190

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0954

Gnomad AMI

AF:

0.581

Gnomad AMR

AF:

0.171

Gnomad ASJ

AF:

0.322

Gnomad EAS

AF:

0.410

Gnomad SAS

AF:

0.188

Gnomad FIN

AF:

0.308

Gnomad MID

AF:

0.137

Gnomad NFE

AF:

0.310

Gnomad OTH

AF:

0.227

GnomAD3 exomes

AF:

0.267

AC:

67168

AN:

251406

Hom.:

10140

AF XY:

0.269

AC XY:

36562

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.0918

Gnomad AMR exome

AF:

0.143

Gnomad ASJ exome

AF:

0.315

Gnomad EAS exome

AF:

0.419

Gnomad SAS exome

AF:

0.188

Gnomad FIN exome

AF:

0.312

Gnomad NFE exome

AF:

0.314

Gnomad OTH exome

AF:

0.271

GnomAD4 exome

AF:

0.302

AC:

437064

AN:

1446726

Hom.:

69352

Cov.:

AF XY:

0.299

AC XY:

215672

AN XY:

720464

show subpopulations

Gnomad4 AFR exome

AF:

0.0847

Gnomad4 AMR exome

AF:

0.147

Gnomad4 ASJ exome

AF:

0.324

Gnomad4 EAS exome

AF:

0.401

Gnomad4 SAS exome

AF:

0.189

Gnomad4 FIN exome

AF:

0.314

Gnomad4 NFE exome

AF:

0.320

Gnomad4 OTH exome

AF:

0.293

GnomAD4 genome

AF:

0.237

AC:

36098

AN:

152158

Hom.:

5183

Cov.:

AF XY:

0.233

AC XY:

17337

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0953

Gnomad4 AMR

AF:

0.171

Gnomad4 ASJ

AF:

0.322

Gnomad4 EAS

AF:

0.409

Gnomad4 SAS

AF:

0.189

Gnomad4 FIN

AF:

0.308

Gnomad4 NFE

AF:

0.310

Gnomad4 OTH

AF:

0.228

Alfa

AF:

0.295

Hom.:

14060

Bravo

AF:

0.227

TwinsUK

AF:

0.337

AC:

1249

ALSPAC

AF:

0.326

AC:

1257

ESP6500AA

AF:

0.104

AC:

456

ESP6500EA

AF:

0.319

AC:

2740

ExAC

AF:

0.269

AC:

32706

Asia WGS

AF:

0.278

AC:

968

AN:

3478

EpiCase

AF:

0.294

EpiControl

AF:

0.290

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.032

T;.;.;T

Eigen

Benign

-0.14

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.81

T;T;T;T

MetaRNN

Benign

0.0032

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.020

N;.;.;.

MutationTaster

Benign

2.5e-7

P;P;P

PrimateAI

Uncertain

0.63

PROVEAN

Benign

1.1

N;N;N;.

REVEL

Benign

0.073

Sift

Benign

0.78

T;T;T;.

Sift4G

Benign

0.73

T;T;T;T

Polyphen

0.0

B;.;.;.

Vest4

0.15

MPC

0.31

ClinPred

0.044

GERP RS

6.1

Varity_R

0.26

gMVP

0.42

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over