rs1052874

chr8-27810202-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018492.4(PBK):c.*103G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 776,534 control chromosomes in the GnomAD database, including 8,800 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (2393 hom., cov: 32)
  • Exomes 𝑓: 0.13 (6407 hom.)
• Consequence: PBK NM_018492.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.478

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]

ESCO2 (HGNC:27230): (establishment of sister chromatid cohesion N-acetyltransferase 2) This gene encodes a protein that may have acetyltransferase activity and may be required for the establishment of sister chromatid cohesion during the S phase of mitosis. Mutations in this gene have been associated with Roberts syndrome. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PBK	NM_018492.4	c.*103G>C		3_prime_UTR_variant	8/8	ENST00000301905.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PBK	ENST00000301905.9	c.*103G>C		3_prime_UTR_variant	8/8	1	NM_018492.4	P1
ESCO2	ENST00000522378.5	c.*862-1103C>G		intron_variant, NMD_transcript_variant		1
PBK	ENST00000522944.5	c.*103G>C		3_prime_UTR_variant	8/8	2

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23934 AN: 151988 Hom.: 2392 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.0859

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0983

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.126 AC: 78950 AN: 624428 Hom.: 6407 Cov.: 8 AF XY: 0.129 AC XY: 43143 AN XY: 334882

Gnomad4 AFR exome AF: 0.248

Gnomad4 AMR exome AF: 0.0981

Gnomad4 ASJ exome AF: 0.190

Gnomad4 EAS exome AF: 0.334

Gnomad4 SAS exome AF: 0.192

Gnomad4 FIN exome AF: 0.0891

Gnomad4 NFE exome AF: 0.0957

Gnomad4 OTH exome AF: 0.145

GnomAD4 genome AF: 0.157 AC: 23942 AN: 152106 Hom.: 2393 Cov.: 32 AF XY: 0.157 AC XY: 11686 AN XY: 74372

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.0859

Gnomad4 NFE AF: 0.0983

Gnomad4 OTH AF: 0.167

Alfa AF: 0.121 Hom.: 186

Bravo AF: 0.164

Asia WGS AF: 0.261 AC: 910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	4.4
Dann	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs1052874; hg19: chr8-27667719; COSMIC: COSV57272767; COSMIC: COSV57272767;