dbSNP rs200124663: POLDIP3:p.Arg246Pro (chr22-42596262-C-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_032311.5(POLDIP3):c.737G>C(p.Arg246Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R246Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

POLDIP3
NM_032311.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.58

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.36131564).

BS2

High AC in GnomAdExome4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032311.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POLDIP3	NM_032311.5	MANE Select	c.737G>C	p.Arg246Pro	missense	Exon 5 of 9	NP_115687.2
POLDIP3	NM_001278657.2		c.788G>C	p.Arg263Pro	missense	Exon 5 of 9	NP_001265586.1	F6VRR5
POLDIP3	NM_178136.3		c.650G>C	p.Arg217Pro	missense	Exon 4 of 8	NP_835237.1	Q9BY77-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POLDIP3	ENST00000252115.10	TSL:1 MANE Select	c.737G>C	p.Arg246Pro	missense	Exon 5 of 9	ENSP00000252115.5	Q9BY77-1
POLDIP3	ENST00000348657.6	TSL:1	c.650G>C	p.Arg217Pro	missense	Exon 4 of 8	ENSP00000252116.5	Q9BY77-2
POLDIP3	ENST00000339677.10	TSL:1	c.450+6508G>C		intron	N/A	ENSP00000343060.6	Q6R954

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000795

AC:

AN:

251480

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111992

Other (OTH)

AF:

0.0000166

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.13

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0021

Eigen

Benign

0.11

Eigen_PC

Benign

0.22

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.018

MetaRNN

Benign

0.36

MetaSVM

Benign

-0.67

MutationAssessor

Uncertain

2.1

PhyloP100

3.6

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.66

REVEL

Benign

0.12

Sift

Benign

0.073

Sift4G

Benign

0.21

Polyphen

0.99

Vest4

0.67

MutPred

0.46

Loss of MoRF binding (P = 0.0053)

MVP

0.64

MPC

0.12

ClinPred

0.43

GERP RS

3.9

Varity_R

0.19

gMVP

0.71

Mutation Taster

=64/36

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over