rs200083664

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

The NM_001345922.3(POLK):c.-378A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,499,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

POLK
NM_001345922.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.229

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021710068).

BS1

Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.0000193 (26/1347160) while in subpopulation EAS AF = 0.000717 (25/34876). AF 95% confidence interval is 0.000497. There are 0 homozygotes in GnomAdExome4. There are 13 alleles in the male GnomAdExome4 subpopulation. Median coverage is 21. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001345922.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POLK	NM_016218.6	MANE Select	c.7A>G	p.Ser3Gly	missense	Exon 2 of 15	NP_057302.1	Q9UBT6-1
POLK	NM_001345922.3		c.-378A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 16	NP_001332851.1	Q9UBT6-8
POLK	NM_001395893.1		c.-378A>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 17	NP_001382822.1	Q9UBT6-8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POLK	ENST00000241436.9	TSL:1 MANE Select	c.7A>G	p.Ser3Gly	missense	Exon 2 of 15	ENSP00000241436.4	Q9UBT6-1
POLK	ENST00000508526.5	TSL:1	c.7A>G	p.Ser3Gly	missense	Exon 1 of 9	ENSP00000426853.1	Q9UBT6-3
POLK	ENST00000515295.5	TSL:1	c.7A>G	p.Ser3Gly	missense	Exon 1 of 10	ENSP00000424174.1	Q9UBT6-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152194

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

GnomAD2 exomes

AF:

0.0000236

AC:

AN:

212158

AF XY:

0.0000345

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000301

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000100

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000193

AC:

AN:

1347160

Hom.:

Cov.:

AF XY:

0.0000194

AC XY:

AN XY:

670824

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29276

American (AMR)

AF:

0.00

AC:

AN:

36982

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23830

East Asian (EAS)

AF:

0.000717

AC:

AN:

34876

South Asian (SAS)

AF:

0.00

AC:

AN:

70974

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51156

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5384

European-Non Finnish (NFE)

AF:

9.62e-7

AC:

AN:

1039092

Other (OTH)

AF:

0.00

AC:

AN:

55590

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41574

American (AMR)

AF:

0.00

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000330

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.54

CADD

Benign

6.6

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.051

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.58

M_CAP

Benign

0.0092

MetaRNN

Benign

0.022

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

0.23

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.35

REVEL

Benign

0.055

Sift

Benign

0.20

Sift4G

Uncertain

0.028

Polyphen

0.0

Vest4

0.027

MVP

0.33

MPC

0.065

ClinPred

0.012

GERP RS

0.17

PromoterAI

0.011

Neutral

(source)

Varity_R

0.032

gMVP

0.088

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over