Genetic Variant ENST00000241436.9:c.28A>G (chr5-75547050-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000241436.9(POLK):c.28A>G(p.Ser10Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S10R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

POLK
ENST00000241436.9 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.547

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07886508).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein
POLK	NM_001387111.3 link	c.28A>G	p.Ser10Gly	missense_variant	Exon 2 of 16	NP_001374040.1
POLK	NM_001395894.1 link	c.28A>G	p.Ser10Gly	missense_variant	Exon 3 of 17	NP_001382823.1
POLK	NM_001395897.1 link	c.28A>G	p.Ser10Gly	missense_variant	Exon 3 of 16	NP_001382826.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLK	ENST00000241436.9 link	c.28A>G	p.Ser10Gly	missense_variant	Exon 2 of 15	1		ENSP00000241436.4		Q9UBT6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000433

AC:

AN:

230922

Hom.:

AF XY:

0.00

AC XY:

AN XY:

125586

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000938

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1380316

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

689186

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

8.2

DANN

Benign

0.97

DEOGEN2

Benign

0.039

T;T;.;.;.

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.54

T;T;T;T;T

M_CAP

Benign

0.0092

MetaRNN

Benign

0.079

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.1

L;.;L;L;L

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.41

N;N;N;N;N

REVEL

Benign

0.067

Sift

Benign

0.068

T;T;T;T;T

Sift4G

Benign

0.21

T;T;T;T;T

Polyphen

0.13

B;.;B;.;P

Vest4

0.046

MutPred

0.14

Loss of phosphorylation at S10 (P = 0.0175);Loss of phosphorylation at S10 (P = 0.0175);Loss of phosphorylation at S10 (P = 0.0175);Loss of phosphorylation at S10 (P = 0.0175);Loss of phosphorylation at S10 (P = 0.0175);

MVP

0.52

MPC

0.065

ClinPred

0.10

GERP RS

2.9

Varity_R

0.029

gMVP

0.077

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over