dbSNP rs28627172: POLDIP3:p.Ala16Val (chr22-42614811-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032311.5(POLDIP3):c.47C>T(p.Ala16Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,613,696 control chromosomes in the GnomAD database, including 15,719 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 2046 hom., cov: 33)

Exomes 𝑓: 0.13 ( 13673 hom. )

Consequence

POLDIP3
NM_032311.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.59

Variant links:

Genes affected

POLDIP3 (HGNC:23782): (DNA polymerase delta interacting protein 3) This gene encodes an RRM (RNA recognition motif)-containing protein that participates in the regulation of translation by recruiting ribosomal protein S6 kinase beta-1 to mRNAs. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

POLDIP3 links:

ENSG00000289517 (HGNC:):

ENSG00000289517 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01321581).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLDIP3	NM_032311.5 link	c.47C>T	p.Ala16Val	missense_variant	Exon 1 of 9	ENST00000252115.10	NP_115687.2	Q9BY77-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
POLDIP3	ENST00000252115.10 link	c.47C>T	p.Ala16Val	missense_variant	Exon 1 of 9	1	NM_032311.5	ENSP00000252115.5	Q9BY77-1
ENSG00000289517	ENST00000617178.5 link	n.*908C>T		non_coding_transcript_exon_variant	Exon 6 of 14	1		ENSP00000482500.2	A0A087WZB1
ENSG00000289517	ENST00000617178.5 link	n.*908C>T		3_prime_UTR_variant	Exon 6 of 14	1		ENSP00000482500.2	A0A087WZB1

Frequencies

GnomAD3 genomes

AF:

0.150

AC:

22838

AN:

152110

Hom.:

2046

Cov.:

show subpopulations

Gnomad AFR

AF:

0.236

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.114

Gnomad ASJ

AF:

0.129

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0818

Gnomad FIN

AF:

0.0955

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.132

Gnomad OTH

AF:

0.155

GnomAD3 exomes

AF:

0.113

AC:

28318

AN:

250988

Hom.:

2016

AF XY:

0.111

AC XY:

15127

AN XY:

135788

show subpopulations

Gnomad AFR exome

AF:

0.234

Gnomad AMR exome

AF:

0.0753

Gnomad ASJ exome

AF:

0.136

Gnomad EAS exome

AF:

0.00131

Gnomad SAS exome

AF:

0.0963

Gnomad FIN exome

AF:

0.0919

Gnomad NFE exome

AF:

0.131

Gnomad OTH exome

AF:

0.119

GnomAD4 exome

AF:

0.131

AC:

191786

AN:

1461468

Hom.:

13673

Cov.:

AF XY:

0.129

AC XY:

93922

AN XY:

727048

show subpopulations

Gnomad4 AFR exome

AF:

0.246

Gnomad4 AMR exome

AF:

0.0811

Gnomad4 ASJ exome

AF:

0.131

Gnomad4 EAS exome

AF:

0.000831

Gnomad4 SAS exome

AF:

0.0970

Gnomad4 FIN exome

AF:

0.0941

Gnomad4 NFE exome

AF:

0.139

Gnomad4 OTH exome

AF:

0.135

GnomAD4 genome

AF:

0.150

AC:

22857

AN:

152228

Hom.:

2046

Cov.:

AF XY:

0.145

AC XY:

10793

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.236

Gnomad4 AMR

AF:

0.114

Gnomad4 ASJ

AF:

0.129

Gnomad4 EAS

AF:

0.00173

Gnomad4 SAS

AF:

0.0816

Gnomad4 FIN

AF:

0.0955

Gnomad4 NFE

AF:

0.132

Gnomad4 OTH

AF:

0.154

Alfa

AF:

0.130

Hom.:

2244

Bravo

AF:

0.155

TwinsUK

AF:

0.138

AC:

512

ALSPAC

AF:

0.151

AC:

582

ESP6500AA

AF:

0.234

AC:

1030

ESP6500EA

AF:

0.139

AC:

1192

ExAC

AF:

0.117

AC:

14150

Asia WGS

AF:

0.0570

AC:

197

AN:

3478

EpiCase

AF:

0.132

EpiControl

AF:

0.132

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0024

.;T;T;T;.

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.70

T;T;T;T;T

MetaRNN

Benign

0.013

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.69

N;N;.;.;.

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.56

N;N;.;.;N

REVEL

Benign

0.033

Sift

Benign

0.10

T;T;.;.;T

Sift4G

Benign

0.31

T;T;T;T;T

Polyphen

0.17

B;B;.;.;P

Vest4

0.13

MPC

0.078

ClinPred

0.0028

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.041

gMVP

0.17

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