Variant rs3213801 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_001387111.3(POLK):c.969C>T(p.Ala323Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,610,014 control chromosomes in the GnomAD database, including 43,187 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 0.22 ( 3906 hom., cov: 32)

Exomes 𝑓: 0.22 ( 39281 hom. )

Consequence

POLK
NM_001387111.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.773

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:

POLK (HGNC:):

POLK links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP7

Synonymous conserved (PhyloP=0.773 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein
POLK	NM_001387111.3 linkuse as main transcript	c.969C>T	p.Ala323Ala	synonymous_variant	8/16	NP_001374040.1
POLK	NM_001395894.1 linkuse as main transcript	c.969C>T	p.Ala323Ala	synonymous_variant	9/17	NP_001382823.1
POLK	NM_001395897.1 linkuse as main transcript	c.966C>T	p.Ala322Ala	synonymous_variant	8/16	NP_001382826.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLK	ENST00000241436.9 linkuse as main transcript	c.927C>T	p.Ala309Ala	synonymous_variant	7/15	1		ENSP00000241436.4		Q9UBT6-1

Frequencies

GnomAD3 genomes

AF:

0.222

AC:

33803

AN:

151942

Hom.:

3901

Cov.:

show subpopulations

Gnomad AFR

AF:

0.218

Gnomad AMI

AF:

0.281

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.267

Gnomad EAS

AF:

0.324

Gnomad SAS

AF:

0.394

Gnomad FIN

AF:

0.234

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.219

GnomAD3 exomes

AF:

0.237

AC:

59418

AN:

250182

Hom.:

7859

AF XY:

0.247

AC XY:

33470

AN XY:

135492

show subpopulations

Gnomad AFR exome

AF:

0.220

Gnomad AMR exome

AF:

0.146

Gnomad ASJ exome

AF:

0.265

Gnomad EAS exome

AF:

0.322

Gnomad SAS exome

AF:

0.392

Gnomad FIN exome

AF:

0.235

Gnomad NFE exome

AF:

0.211

Gnomad OTH exome

AF:

0.230

GnomAD4 exome

AF:

0.225

AC:

328007

AN:

1457954

Hom.:

39281

Cov.:

AF XY:

0.231

AC XY:

167292

AN XY:

725558

show subpopulations

Gnomad4 AFR exome

AF:

0.223

Gnomad4 AMR exome

AF:

0.151

Gnomad4 ASJ exome

AF:

0.265

Gnomad4 EAS exome

AF:

0.338

Gnomad4 SAS exome

AF:

0.389

Gnomad4 FIN exome

AF:

0.234

Gnomad4 NFE exome

AF:

0.209

Gnomad4 OTH exome

AF:

0.228

GnomAD4 genome

AF:

0.222

AC:

33828

AN:

152060

Hom.:

3906

Cov.:

AF XY:

0.227

AC XY:

16889

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.219

Gnomad4 AMR

AF:

0.186

Gnomad4 ASJ

AF:

0.267

Gnomad4 EAS

AF:

0.324

Gnomad4 SAS

AF:

0.395

Gnomad4 FIN

AF:

0.234

Gnomad4 NFE

AF:

0.209

Gnomad4 OTH

AF:

0.216

Alfa

AF:

0.217

Hom.:

6011

Bravo

AF:

0.215

Asia WGS

AF:

0.335

AC:

1163

AN:

3478

EpiCase

AF:

0.218

EpiControl

AF:

0.214

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over