Variant rs487848 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_199420.4(POLQ):c.1742C>T(p.Ala581Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.067 in 1,613,052 control chromosomes in the GnomAD database, including 4,726 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.098 ( 1068 hom., cov: 32)

Exomes 𝑓: 0.064 ( 3658 hom. )

Consequence

POLQ
NM_199420.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 7.59

Variant links:

Genes affected

POLQ (HGNC:9186): (DNA polymerase theta) Enables catalytic activity, acting on DNA; chromatin binding activity; and identical protein binding activity. Involved in DNA repair; negative regulation of double-strand break repair via homologous recombination; and protein homooligomerization. Located in Golgi apparatus; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

POLQ links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018025637).

BP6

Variant 3-121510113-G-A is Benign according to our data. Variant chr3-121510113-G-A is described in ClinVar as [Benign]. Clinvar id is 3056620.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLQ	NM_199420.4 linkuse as main transcript	c.1742C>T	p.Ala581Val	missense_variant	11/30	ENST00000264233.6	NP_955452.3	O75417-1Q59EE4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLQ	ENST00000264233.6 linkuse as main transcript	c.1742C>T	p.Ala581Val	missense_variant	11/30	1	NM_199420.4	ENSP00000264233.5		O75417-1

Frequencies

GnomAD3 genomes

AF:

0.0982

AC:

14914

AN:

151946

Hom.:

1063

Cov.:

show subpopulations

Gnomad AFR

AF:

0.196

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.0626

Gnomad ASJ

AF:

0.0784

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0112

Gnomad FIN

AF:

0.0594

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0689

Gnomad OTH

AF:

0.0951

GnomAD3 exomes

AF:

0.0617

AC:

15505

AN:

251438

Hom.:

738

AF XY:

0.0572

AC XY:

7771

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.202

Gnomad AMR exome

AF:

0.0413

Gnomad ASJ exome

AF:

0.0784

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0131

Gnomad FIN exome

AF:

0.0559

Gnomad NFE exome

AF:

0.0705

Gnomad OTH exome

AF:

0.0623

GnomAD4 exome

AF:

0.0637

AC:

93100

AN:

1460988

Hom.:

3658

Cov.:

AF XY:

0.0619

AC XY:

44974

AN XY:

726858

show subpopulations

Gnomad4 AFR exome

AF:

0.205

Gnomad4 AMR exome

AF:

0.0437

Gnomad4 ASJ exome

AF:

0.0786

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0135

Gnomad4 FIN exome

AF:

0.0580

Gnomad4 NFE exome

AF:

0.0663

Gnomad4 OTH exome

AF:

0.0656

GnomAD4 genome

AF:

0.0982

AC:

14939

AN:

152064

Hom.:

1068

Cov.:

AF XY:

0.0954

AC XY:

7091

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.196

Gnomad4 AMR

AF:

0.0625

Gnomad4 ASJ

AF:

0.0784

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0106

Gnomad4 FIN

AF:

0.0594

Gnomad4 NFE

AF:

0.0689

Gnomad4 OTH

AF:

0.0941

Alfa

AF:

0.0725

Hom.:

1084

Bravo

AF:

0.103

TwinsUK

AF:

0.0688

AC:

255

ALSPAC

AF:

0.0649

AC:

250

ESP6500AA

AF:

0.202

AC:

888

ESP6500EA

AF:

0.0637

AC:

548

ExAC

AF:

0.0654

AC:

7934

Asia WGS

AF:

0.0260

AC:

AN:

3478

EpiCase

AF:

0.0695

EpiControl

AF:

0.0660

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

POLQ-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.090

.;T

Eigen

Benign

0.11

Eigen_PC

Benign

0.18

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

D;D

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

2.9

.;M

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.1

.;D

REVEL

Benign

0.14

Sift

Benign

0.15

.;T

Sift4G

Uncertain

0.046

D;T

Polyphen

0.47

.;P

Vest4

0.12

MPC

0.12

ClinPred

0.060

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.24

gMVP

0.45

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over