ENST00000241436.9:c.1284G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PP5_ModerateBP4BP7

The ENST00000241436.9(POLK):​c.1284G>A​(p.Ala428Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000207 in 1,596,492 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 Pathogenic (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

POLK
ENST00000241436.9 synonymous

Scores

2

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 1.79

Publications

6 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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PP5
Variant 5-75590368-G-A is Pathogenic according to our data. Variant chr5-75590368-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 218217.Status of the report is criteria_provided_single_submitter, 1 stars.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.32). . Strength limited to SUPPORTING due to the PP5.
BP7
Synonymous conserved (PhyloP=1.79 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
POLKNM_001387111.3 linkc.1326G>A p.Ala442Ala synonymous_variant Exon 12 of 16 NP_001374040.1
POLKNM_001395894.1 linkc.1326G>A p.Ala442Ala synonymous_variant Exon 13 of 17 NP_001382823.1
POLKNM_001395897.1 linkc.1323G>A p.Ala441Ala synonymous_variant Exon 12 of 16 NP_001382826.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
POLKENST00000241436.9 linkc.1284G>A p.Ala428Ala synonymous_variant Exon 11 of 15 1 ENSP00000241436.4 Q9UBT6-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152106
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000243
AC:
6
AN:
246956
AF XY:
0.0000299
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000891
Gnomad OTH exome
AF:
0.000166
GnomAD4 exome
AF:
0.0000215
AC:
31
AN:
1444386
Hom.:
0
Cov.:
27
AF XY:
0.0000209
AC XY:
15
AN XY:
718696
show subpopulations
African (AFR)
AF:
0.0000303
AC:
1
AN:
32978
American (AMR)
AF:
0.00
AC:
0
AN:
43266
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25598
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39498
South Asian (SAS)
AF:
0.000179
AC:
15
AN:
83972
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52808
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5690
European-Non Finnish (NFE)
AF:
0.00000908
AC:
10
AN:
1100984
Other (OTH)
AF:
0.0000839
AC:
5
AN:
59592
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.454
Heterozygous variant carriers
0
2
4
6
8
10
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.0000131
AC:
2
AN:
152106
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74284
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.0000242
AC:
1
AN:
41406
American (AMR)
AF:
0.00
AC:
0
AN:
15270
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5196
South Asian (SAS)
AF:
0.000207
AC:
1
AN:
4832
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10600
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68010
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000203), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.000130
Hom.:
0
Bravo
AF:
0.0000189

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Prostate cancer Pathogenic:1
Jan 01, 2013
Tulane Cancer Center, Tulane University
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.32
CADD
Benign
13
DANN
Benign
0.59
PhyloP100
1.8
Mutation Taster
=99/1
disease causing (ClinVar)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs770984846; hg19: chr5-74886193; COSMIC: COSV54034895; API