Variant rs148960463 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000241436.9(POLK):c.85G>A(p.Glu29Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00197 in 1,540,640 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0020 ( 7 hom. )

Consequence

POLK
ENST00000241436.9 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1B:1

Conservation

PhyloP100: 5.07

Variant links:

Genes affected

POLK (HGNC:9183): (DNA polymerase kappa) This gene encodes a member of the DNA polymerase type-Y family of proteins. The encoded protein is a specialized DNA polymerase that catalyzes translesion DNA synthesis, which allows DNA replication in the presence of DNA lesions. Human cell lines lacking a functional copy of this gene exhibit impaired genome integrity and enhanced susceptibility to oxidative damage. Mutations in this gene that impair enzyme activity may be associated with prostate cancer in human patients. [provided by RefSeq, Sep 2016]

POLK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010744542).

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLK	NM_016218.6 linkuse as main transcript	c.85G>A	p.Glu29Lys	missense_variant	2/15	ENST00000241436.9	NP_057302.1
POLK	NR_170560.3 linkuse as main transcript	n.259G>A		non_coding_transcript_exon_variant	3/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLK	ENST00000241436.9 linkuse as main transcript	c.85G>A	p.Glu29Lys	missense_variant	2/15	1	NM_016218.6	ENSP00000241436	P1	Q9UBT6-1

Frequencies

GnomAD3 genomes

AF:

0.00141

AC:

215

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00456

Gnomad FIN

AF:

0.000942

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00228

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00210

AC:

498

AN:

236644

Hom.:

AF XY:

0.00239

AC XY:

307

AN XY:

128402

show subpopulations

Gnomad AFR exome

AF:

0.000336

Gnomad AMR exome

AF:

0.000999

Gnomad ASJ exome

AF:

0.000408

Gnomad EAS exome

AF:

0.0000599

Gnomad SAS exome

AF:

0.00487

Gnomad FIN exome

AF:

0.00116

Gnomad NFE exome

AF:

0.00261

Gnomad OTH exome

AF:

0.00178

GnomAD4 exome

AF:

0.00204

AC:

2826

AN:

1388352

Hom.:

Cov.:

AF XY:

0.00213

AC XY:

1477

AN XY:

692942

show subpopulations

Gnomad4 AFR exome

AF:

0.000255

Gnomad4 AMR exome

AF:

0.00114

Gnomad4 ASJ exome

AF:

0.000753

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00516

Gnomad4 FIN exome

AF:

0.00108

Gnomad4 NFE exome

AF:

0.00207

Gnomad4 OTH exome

AF:

0.00151

GnomAD4 genome

AF:

0.00141

AC:

215

AN:

152288

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

107

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.000942

Gnomad4 NFE

AF:

0.00228

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00200

Hom.:

Bravo

AF:

0.00112

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00198

AC:

ExAC

AF:

0.00219

AC:

266

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Malignant tumor of prostate

Pathogenic:1

Pathogenic, criteria provided, single submitter

research

Tulane Cancer Center, Tulane University

Nov 06, 2013

- -

Seizure;C4022738:Neurodevelopmental delay

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Institute of Human Genetics, University of Leipzig Medical Center

Feb 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.20

T;T;.;.;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.97

D;D;D;D;D

M_CAP

Benign

0.024

MetaRNN

Benign

0.011

T;T;T;T;T

MetaSVM

Benign

-0.53

MutationAssessor

Uncertain

2.0

M;.;M;M;M

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-2.3

N;D;N;N;N

REVEL

Benign

0.17

Sift

Uncertain

0.027

D;T;T;T;T

Sift4G

Uncertain

0.060

T;D;T;T;T

Polyphen

0.96

D;.;P;.;P

Vest4

0.31

MVP

0.64

MPC

0.13

ClinPred

0.74

GERP RS

5.6

Varity_R

0.75

gMVP

0.27

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