22-42585900-G-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_032311.5(POLDIP3):​c.1157C>G​(p.Ser386Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000316 in 1,613,360 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.

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.000034 ( 0 hom. )

Consequence

POLDIP3
NM_032311.5 missense

Scores

1
5
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.13
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.2040745).
BS2
High AC in GnomAdExome4 at 49 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
POLDIP3NM_032311.5 linkc.1157C>G p.Ser386Cys missense_variant Exon 9 of 9 ENST00000252115.10 NP_115687.2 Q9BY77-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
POLDIP3ENST00000252115.10 linkc.1157C>G p.Ser386Cys missense_variant Exon 9 of 9 1 NM_032311.5 ENSP00000252115.5 Q9BY77-1
ENSG00000289517ENST00000617178.5 linkn.*2018C>G non_coding_transcript_exon_variant Exon 14 of 14 1 ENSP00000482500.2 A0A087WZB1
ENSG00000289517ENST00000617178.5 linkn.*2018C>G 3_prime_UTR_variant Exon 14 of 14 1 ENSP00000482500.2 A0A087WZB1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152166
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000279
AC:
7
AN:
251254
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135812
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:
0.0000616
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000335
AC:
49
AN:
1461194
Hom.:
0
Cov.:
31
AF XY:
0.0000385
AC XY:
28
AN XY:
726916
show subpopulations
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:
0.0000441
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152166
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000731
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.089
BayesDel_addAF
Benign
-0.077
T
BayesDel_noAF
Benign
-0.16
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.037
.;T;T
Eigen
Uncertain
0.31
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.83
T;T;T
M_CAP
Benign
0.0092
T
MetaRNN
Benign
0.20
T;T;T
MetaSVM
Benign
-0.62
T
MutationAssessor
Benign
1.6
.;L;.
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-1.7
N;N;.
REVEL
Benign
0.23
Sift
Uncertain
0.0010
D;D;.
Sift4G
Uncertain
0.012
D;D;D
Polyphen
1.0
D;D;.
Vest4
0.33
MutPred
0.39
.;Loss of phosphorylation at S386 (P = 0.0147);.;
MVP
0.44
MPC
0.025
ClinPred
0.40
T
GERP RS
4.7
Varity_R
0.20
gMVP
0.64

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.

Other links and lift over

dbSNP: rs775980413; hg19: chr22-42981906; API