ENST00000241436.9:c.1284G>A
Variant names:
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
ENST00000241436.9 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.79
Publications
6 publications found
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 |
---|---|---|---|---|---|---|---|---|
POLK | NM_001387111.3 | c.1326G>A | p.Ala442Ala | synonymous_variant | Exon 12 of 16 | NP_001374040.1 | ||
POLK | NM_001395894.1 | c.1326G>A | p.Ala442Ala | synonymous_variant | Exon 13 of 17 | NP_001382823.1 | ||
POLK | NM_001395897.1 | c.1323G>A | p.Ala441Ala | synonymous_variant | Exon 12 of 16 | NP_001382826.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152106Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
2
AN:
152106
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
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Gnomad ASJ
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Gnomad EAS
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Gnomad FIN
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Gnomad MID
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Gnomad NFE
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Gnomad OTH
AF:
GnomAD2 exomes AF: 0.0000243 AC: 6AN: 246956 AF XY: 0.0000299 show subpopulations
GnomAD2 exomes
AF:
AC:
6
AN:
246956
AF XY:
Gnomad AFR exome
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Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.0000215 AC: 31AN: 1444386Hom.: 0 Cov.: 27 AF XY: 0.0000209 AC XY: 15AN XY: 718696 show subpopulations
GnomAD4 exome
AF:
AC:
31
AN:
1444386
Hom.:
Cov.:
27
AF XY:
AC XY:
15
AN XY:
718696
show subpopulations
African (AFR)
AF:
AC:
1
AN:
32978
American (AMR)
AF:
AC:
0
AN:
43266
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25598
East Asian (EAS)
AF:
AC:
0
AN:
39498
South Asian (SAS)
AF:
AC:
15
AN:
83972
European-Finnish (FIN)
AF:
AC:
0
AN:
52808
Middle Eastern (MID)
AF:
AC:
0
AN:
5690
European-Non Finnish (NFE)
AF:
AC:
10
AN:
1100984
Other (OTH)
AF:
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
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152106Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74284 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
2
AN:
152106
Hom.:
Cov.:
32
AF XY:
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:
AC:
1
AN:
41406
American (AMR)
AF:
AC:
0
AN:
15270
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5196
South Asian (SAS)
AF:
AC:
1
AN:
4832
European-Finnish (FIN)
AF:
AC:
0
AN:
10600
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68010
Other (OTH)
AF:
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
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Age
Alfa
AF:
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Bravo
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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
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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