8-27823150-A-G

Variant summary

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

The NM_018492.4(PBK):ā€‹c.208T>Cā€‹(p.Cys70Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000431 in 1,552,960 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000053 ( 0 hom., cov: 33)
Exomes š‘“: 0.000042 ( 1 hom. )

Consequence

PBK
NM_018492.4 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.51
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]

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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=0.08346692).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PBKNM_018492.4 linkc.208T>C p.Cys70Arg missense_variant 4/8 ENST00000301905.9 NP_060962.2 Q96KB5-1V9HWH0
PBKNM_001278945.2 linkc.208T>C p.Cys70Arg missense_variant 4/8 NP_001265874.1 Q96KB5-2
PBKNM_001363040.2 linkc.208T>C p.Cys70Arg missense_variant 4/8 NP_001349969.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PBKENST00000301905.9 linkc.208T>C p.Cys70Arg missense_variant 4/81 NM_018492.4 ENSP00000301905.4 Q96KB5-1
PBKENST00000522944.5 linkc.208T>C p.Cys70Arg missense_variant 4/82 ENSP00000428489.1 Q96KB5-2
PBKENST00000521226.2 linkc.106T>C p.Cys36Arg missense_variant 4/63 ENSP00000427892.2 E5RFX4
PBKENST00000524266.1 linkn.153-2456T>C intron_variant 5 ENSP00000428438.1 E5RIE1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152122
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00115
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:
0.000134
AC:
33
AN:
246714
Hom.:
0
AF XY:
0.000120
AC XY:
16
AN XY:
133516
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000302
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00138
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000356
Gnomad OTH exome
AF:
0.000502
GnomAD4 exome
AF:
0.0000421
AC:
59
AN:
1400838
Hom.:
1
Cov.:
22
AF XY:
0.0000371
AC XY:
26
AN XY:
700204
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000227
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000486
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000142
Gnomad4 OTH exome
AF:
0.000378
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152122
Hom.:
0
Cov.:
33
AF XY:
0.0000538
AC XY:
4
AN XY:
74300
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00115
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000676
Hom.:
0
Bravo
AF:
0.0000642
ExAC
AF:
0.000132
AC:
16
Asia WGS
AF:
0.000579
AC:
2
AN:
3468

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 submitterclinical testingAmbry GeneticsJul 20, 2021The c.208T>C (p.C70R) alteration is located in exon 4 (coding exon 3) of the PBK gene. This alteration results from a T to C substitution at nucleotide position 208, causing the cysteine (C) at amino acid position 70 to be replaced by an arginine (R). 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
0.51
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Uncertain
0.030
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.12
T;.;.
Eigen
Uncertain
0.19
Eigen_PC
Uncertain
0.30
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.66
T;T;T
M_CAP
Benign
0.036
D
MetaRNN
Benign
0.083
T;T;T
MetaSVM
Benign
-0.80
T
MutationAssessor
Benign
1.5
L;L;.
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-2.0
N;N;.
REVEL
Benign
0.27
Sift
Uncertain
0.017
D;D;.
Sift4G
Benign
0.20
T;T;.
Polyphen
0.30
B;.;.
Vest4
0.83
MutPred
0.51
Gain of solvent accessibility (P = 0.0078);Gain of solvent accessibility (P = 0.0078);.;
MVP
0.82
MPC
0.60
ClinPred
0.15
T
GERP RS
6.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.55
gMVP
0.83

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.

Other links and lift over

dbSNP: rs367624592; hg19: chr8-27680667; API