Variant 4-25234287-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018323.4(PI4K2B):c.124G>T(p.Ala42Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,418,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000071 ( 0 hom. )

Consequence

PI4K2B
NM_018323.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.38

Variant links:

Genes affected

PI4K2B (HGNC:18215): (phosphatidylinositol 4-kinase type 2 beta) This gene encodes a member of the type II PI4 kinase protein family. The encoded protein is primarily cytosolic and contributes to overall PI4-kinase activity along with other protein family members. This protein is involved in early T cell activation. [provided by RefSeq, Dec 2016]

PI4K2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10272616).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PI4K2B	NM_018323.4 linkuse as main transcript	c.124G>T	p.Ala42Ser	missense_variant	1/10	ENST00000264864.8
PI4K2B	XM_005248174.3 linkuse as main transcript	c.124G>T	p.Ala42Ser	missense_variant	1/10
PI4K2B	NR_144633.2 linkuse as main transcript	n.255G>T		non_coding_transcript_exon_variant	1/10
PI4K2B	XR_007057941.1 linkuse as main transcript	n.255G>T		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PI4K2B	ENST00000264864.8 linkuse as main transcript	c.124G>T	p.Ala42Ser	missense_variant	1/10	1	NM_018323.4
PI4K2B	ENST00000512921.4 linkuse as main transcript	c.-20-18034G>T		intron_variant		2		P1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000163

AC:

AN:

61392

Hom.:

AF XY:

0.0000284

AC XY:

AN XY:

35258

show subpopulations

Gnomad AFR exome

AF:

0.00122

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000711

AC:

AN:

1266442

Hom.:

Cov.:

AF XY:

0.00000646

AC XY:

AN XY:

618802

show subpopulations

Gnomad4 AFR exome

AF:

0.000306

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000138

AC:

AN:

152116

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.000507

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000140

ExAC

AF:

0.0000129

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

Oct 22, 2021

The c.124G>T (p.A42S) alteration is located in exon 1 (coding exon 1) of the PI4K2B gene. This alteration results from a G to T substitution at nucleotide position 124, causing the alanine (A) at amino acid position 42 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

0.096

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0030

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.66

M_CAP

Pathogenic

0.38

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

0.090

REVEL

Benign

0.067

Sift

Uncertain

0.0090

Sift4G

Benign

0.62

Polyphen

0.88

Vest4

0.17

MutPred

0.24

Gain of glycosylation at S45 (P = 0.0763);

MVP

0.50

MPC

1.0

ClinPred

0.20

GERP RS

2.4

Varity_R

0.14

gMVP

0.12

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