Genetic Variant NM_018323.4:c.49A>T (chr4-25234212-A-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_018323.4(PI4K2B):c.49A>T(p.Ser17Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000213 in 1,410,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

PI4K2B
NM_018323.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0900

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity P4K2B_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15897653).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018323.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PI4K2B	NM_018323.4	MANE Select	c.49A>T	p.Ser17Cys	missense	Exon 1 of 10	NP_060793.2	Q8TCG2
	PI4K2B	NR_144633.2		n.180A>T		non_coding_transcript_exon	Exon 1 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PI4K2B	ENST00000264864.8	TSL:1 MANE Select	c.49A>T	p.Ser17Cys	missense	Exon 1 of 10	ENSP00000264864.6	Q8TCG2
PI4K2B	ENST00000871538.1		c.49A>T	p.Ser17Cys	missense	Exon 1 of 11	ENSP00000541597.1
PI4K2B	ENST00000963199.1		c.49A>T	p.Ser17Cys	missense	Exon 1 of 10	ENSP00000633258.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000159

AC:

AN:

1258338

Hom.:

Cov.:

AF XY:

0.00000325

AC XY:

AN XY:

614668

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25760

American (AMR)

AF:

0.00

AC:

AN:

19806

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19576

East Asian (EAS)

AF:

0.00

AC:

AN:

28114

South Asian (SAS)

AF:

0.00

AC:

AN:

61764

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33476

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4444

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1013660

Other (OTH)

AF:

0.0000387

AC:

AN:

51738

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41442

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000207

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68000

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.012

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.45

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.81

PhyloP100

0.090

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.1

REVEL

Benign

0.13

Sift

Uncertain

0.028

Sift4G

Uncertain

0.028

Polyphen

0.95

Vest4

0.21

MutPred

0.29

Gain of glycosylation at S17 (P = 0.0076)

MVP

0.39

MPC

0.93

ClinPred

0.75

GERP RS

-2.3

PromoterAI

-0.041

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.11

gMVP

0.10

Mutation Taster

=94/6

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over