NM_032311.5:c.47C>T

Variant names:

• chr22-42614811-G-A
• rs28627172
• NM_032311.5:c.47C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 13/20 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59
• Publications: 18 publications found

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]

ENSG00000289517 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLDIP3	NM_032311.5	MANE Select	c.47C>T	p.Ala16Val	missense	Exon 1 of 9	NP_115687.2
	POLDIP3	NM_001278657.2		c.47C>T	p.Ala16Val	missense	Exon 1 of 9	NP_001265586.1	F6VRR5
	POLDIP3	NM_178136.3		c.47C>T	p.Ala16Val	missense	Exon 1 of 8	NP_835237.1	Q9BY77-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLDIP3	ENST00000252115.10	TSL:1 MANE Select	c.47C>T	p.Ala16Val	missense	Exon 1 of 9	ENSP00000252115.5	Q9BY77-1
	POLDIP3	ENST00000348657.6	TSL:1	c.47C>T	p.Ala16Val	missense	Exon 1 of 8	ENSP00000252116.5	Q9BY77-2
	POLDIP3	ENST00000339677.10	TSL:1	c.47C>T	p.Ala16Val	missense	Exon 1 of 3	ENSP00000343060.6	Q6R954

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22838 AN: 152110 Hom.: 2046 Cov.: 33

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

GnomAD2 exomes AF: 0.113 AC: 28318 AN: 250988 AF XY: 0.111

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 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.: 32 AF XY: 0.129 AC XY: 93922 AN XY: 727048

African (AFR) AF: 0.246 AC: 8239 AN: 33460

American (AMR) AF: 0.0811 AC: 3629 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 3418 AN: 26128

East Asian (EAS) AF: 0.000831 AC: 33 AN: 39692

South Asian (SAS) AF: 0.0970 AC: 8368 AN: 86248

European-Finnish (FIN) AF: 0.0941 AC: 5023 AN: 53368

Middle Eastern (MID) AF: 0.159 AC: 919 AN: 5766

European-Non Finnish (NFE) AF: 0.139 AC: 153981 AN: 1111706

Other (OTH) AF: 0.135 AC: 8176 AN: 60380

GnomAD4 genome AF: 0.150 AC: 22857 AN: 152228 Hom.: 2046 Cov.: 33 AF XY: 0.145 AC XY: 10793 AN XY: 74444

African (AFR) AF: 0.236 AC: 9809 AN: 41532

American (AMR) AF: 0.114 AC: 1748 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 447 AN: 3472

East Asian (EAS) AF: 0.00173 AC: 9 AN: 5188

South Asian (SAS) AF: 0.0816 AC: 394 AN: 4826

European-Finnish (FIN) AF: 0.0955 AC: 1013 AN: 10610

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 9005 AN: 67992

Other (OTH) AF: 0.154 AC: 324 AN: 2106

Alfa AF: 0.132 Hom.: 3144

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.6
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.033
Sift	Benign	0.10	T
Sift4G	Benign	0.31	T
Polyphen		0.17	B
Vest4		0.13
MPC		0.078
ClinPred		0.0028	T
GERP RS		3.4
PromoterAI		-0.082	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.041
gMVP		0.17
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs28627172; hg19: chr22-43010817; COSMIC: COSV52808000; COSMIC: COSV52808000;