Variant chr8-27823203-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_018492.4(PBK):c.155C>T(p.Ser52Phe) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000134 in 1,488,200 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

PBK
NM_018492.4 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.70

Variant links:

Genes affected

PBK (HGNC:18282): (PDZ binding kinase) This gene encodes a serine/threonine protein kinase related to the dual specific mitogen-activated protein kinase kinase (MAPKK) family. Evidence suggests that mitotic phosphorylation is required for its catalytic activity. The encoded protein may be involved in the activation of lymphoid cells and support testicular functions, with a suggested role in the process of spermatogenesis. Overexpression of this gene has been implicated in tumorigenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

PBK links:

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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
PBK	NM_018492.4 linkuse as main transcript	c.155C>T	p.Ser52Phe	missense_variant, splice_region_variant	4/8	ENST00000301905.9	NP_060962.2	Q96KB5-1V9HWH0
PBK	NM_001278945.2 linkuse as main transcript	c.155C>T	p.Ser52Phe	missense_variant, splice_region_variant	4/8		NP_001265874.1	Q96KB5-2
PBK	NM_001363040.2 linkuse as main transcript	c.155C>T	p.Ser52Phe	missense_variant, splice_region_variant	4/8		NP_001349969.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PBK	ENST00000301905.9 linkuse as main transcript	c.155C>T	p.Ser52Phe	missense_variant, splice_region_variant	4/8	1	NM_018492.4	ENSP00000301905.4	Q96KB5-1
PBK	ENST00000522944.5 linkuse as main transcript	c.155C>T	p.Ser52Phe	missense_variant, splice_region_variant	4/8	2		ENSP00000428489.1	Q96KB5-2
PBK	ENST00000521226.2 linkuse as main transcript	c.53C>T	p.Ser18Phe	missense_variant, splice_region_variant	4/6	3		ENSP00000427892.2	E5RFX4
PBK	ENST00000524266.1 linkuse as main transcript	n.153-2509C>T		intron_variant		5		ENSP00000428438.1	E5RIE1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151984

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:

0.000192

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

GnomAD4 exome

AF:

7.48e-7

AC:

AN:

1336216

Hom.:

Cov.:

AF XY:

0.00000150

AC XY:

AN XY:

667902

show subpopulations

Gnomad4 AFR exome

AF:

0.0000350

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:

0.00000658

AC:

AN:

151984

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

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

Dec 07, 2021

The c.155C>T (p.S52F) alteration is located in exon 4 (coding exon 3) of the PBK gene. This alteration results from a C to T substitution at nucleotide position 155, causing the serine (S) at amino acid position 52 to be replaced by a phenylalanine (F). 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

Uncertain

0.53

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

T;.;.

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.029

MetaRNN

Uncertain

0.72

D;D;D

MetaSVM

Benign

-0.39

MutationAssessor

Benign

2.0

M;M;.

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-5.1

D;D;.

REVEL

Uncertain

0.47

Sift

Uncertain

0.0040

D;D;.

Sift4G

Uncertain

0.0070

D;D;.

Polyphen

0.99

D;.;.

Vest4

0.73

MutPred

0.53

Loss of disorder (P = 0.0065);Loss of disorder (P = 0.0065);.;

MVP

0.88

MPC

0.46

ClinPred

0.99

GERP RS

6.0

Varity_R

0.75

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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