Variant 11-74618796-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_006591.3(POLD3):c.652G>A(p.Val218Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000396 in 1,610,286 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 3 hom. )

Consequence

POLD3
NM_006591.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.83

Variant links:

Genes affected

POLD3 (HGNC:20932): (DNA polymerase delta 3, accessory subunit) This gene encodes the 66-kDa subunit of DNA polymerase delta. DNA polymerase delta possesses both polymerase and 3' to 5' exonuclease activity and plays a critical role in DNA replication and repair. The encoded protein plays a role in regulating the activity of DNA polymerase delta through interactions with other subunits and the processivity cofactor proliferating cell nuclear antigen (PCNA). Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Mar 2012]

POLD3 links:

POLD3 (HGNC:):

POLD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003626883).

BP6

Variant 11-74618796-G-A is Benign according to our data. Variant chr11-74618796-G-A is described in ClinVar as [Benign]. Clinvar id is 3052473.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLD3	NM_006591.3 linkuse as main transcript	c.652G>A	p.Val218Ile	missense_variant	6/12	ENST00000263681.7	NP_006582.1	Q15054-1A0A024R5M8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
POLD3	ENST00000263681.7 linkuse as main transcript	c.652G>A	p.Val218Ile	missense_variant	6/12	1	NM_006591.3	ENSP00000263681.2	Q15054-1
POLD3	ENST00000527458.5 linkuse as main transcript	c.535G>A	p.Val179Ile	missense_variant	6/12	1		ENSP00000432951.1	Q15054-2
POLD3	ENST00000532497.5 linkuse as main transcript	c.334G>A	p.Val112Ile	missense_variant	5/11	1		ENSP00000436018.1	Q15054-3
POLD3	ENST00000530511.5 linkuse as main transcript	c.*26G>A		downstream_gene_variant		3		ENSP00000432233.1	E9PRK3

Frequencies

GnomAD3 genomes

AF:

0.00216

AC:

329

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00745

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000596

AC:

149

AN:

250024

Hom.:

AF XY:

0.000429

AC XY:

AN XY:

135214

show subpopulations

Gnomad AFR exome

AF:

0.00727

Gnomad AMR exome

AF:

0.000786

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:

0.0000265

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000211

AC:

307

AN:

1457954

Hom.:

Cov.:

AF XY:

0.000159

AC XY:

115

AN XY:

724604

show subpopulations

Gnomad4 AFR exome

AF:

0.00746

Gnomad4 AMR exome

AF:

0.000673

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:

0.00000270

Gnomad4 OTH exome

AF:

0.000398

GnomAD4 genome

AF:

0.00217

AC:

330

AN:

152332

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

151

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00746

Gnomad4 AMR

AF:

0.000981

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000380

Hom.:

Bravo

AF:

0.00214

ESP6500AA

AF:

0.00455

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000700

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

POLD3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 05, 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

0.071

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.094

T;.;.

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.65

T;T;T

M_CAP

Benign

0.0077

MetaRNN

Benign

0.0036

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;.;.

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.37

N;N;N

REVEL

Benign

0.030

Sift

Benign

0.084

T;T;T

Sift4G

Benign

0.21

T;T;T

Polyphen

0.42

B;.;.

Vest4

0.034

MVP

0.41

MPC

0.11

ClinPred

0.013

GERP RS

3.5

Varity_R

0.023

gMVP

0.064

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