NM_152683.4:c.1518T>G

Variant names:

• chr4-184694614-T-G
• rs3184982
• NM_152683.4:c.1518T>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_152683.4(PRIMPOL):​c.1518T>G​(p.Gly506Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,612,878 control chromosomes in the GnomAD database, including 20,383 homozygotes. 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: 𝑓 0.18 (2779 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17604 hom.)
• Consequence: PRIMPOL NM_152683.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.691
• Publications: 18 publications found

Genes affected

PRIMPOL (HGNC:26575): (primase and DNA directed polymerase) This gene encodes a DNA primase-polymerase that belongs to a superfamily of archaeao-eukaryotic primases. Members of this family have primase activity, catalyzing the synthesis of short RNA primers that serve as starting points for DNA synthesis, as well as DNA polymerase activity. The encoded protein facilitates DNA damage tolerance by mediating uninterrupted fork progression after UV irradiation and reinitiating DNA synthesis. An allelic variant in this gene is associated with myopia 22. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

CENPU (HGNC:21348): (centromere protein U) The centromere is a specialized chromatin domain, present throughout the cell cycle, that acts as a platform on which the transient assembly of the kinetochore occurs during mitosis. All active centromeres are characterized by the presence of long arrays of nucleosomes in which CENPA (MIM 117139) replaces histone H3 (see MIM 601128). MLF1IP, or CENPU, is an additional factor required for centromere assembly (Foltz et al., 2006 [PubMed 16622419]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-0.691 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152683.4. 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
	PRIMPOL	NM_152683.4	MANE Select	c.1518T>G	p.Gly506Gly	synonymous	Exon 14 of 14	NP_689896.1	Q96LW4-1
	CENPU	NM_024629.4	MANE Select	c.*674A>C		3_prime_UTR	Exon 13 of 13	NP_078905.2
	PRIMPOL	NM_001345891.2		c.1557T>G	p.Gly519Gly	synonymous	Exon 15 of 15	NP_001332820.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRIMPOL	ENST00000314970.11	TSL:1 MANE Select	c.1518T>G	p.Gly506Gly	synonymous	Exon 14 of 14	ENSP00000313816.6	Q96LW4-1
	PRIMPOL	ENST00000512834.5	TSL:1	c.1515T>G	p.Gly505Gly	synonymous	Exon 14 of 14	ENSP00000425316.1	Q96LW4-2
	PRIMPOL	ENST00000515774.5	TSL:1	c.1131T>G	p.Gly377Gly	synonymous	Exon 13 of 13	ENSP00000421913.1	A0A5S6SZ32

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27390 AN: 151930 Hom.: 2776 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.191

GnomAD2 exomes AF: 0.144 AC: 36018 AN: 250094 AF XY: 0.144

Gnomad AFR exome AF: 0.274

Gnomad AMR exome AF: 0.128

Gnomad ASJ exome AF: 0.170

Gnomad EAS exome AF: 0.000489

Gnomad FIN exome AF: 0.149

Gnomad NFE exome AF: 0.157

Gnomad OTH exome AF: 0.148

GnomAD4 exome AF: 0.151 AC: 219950 AN: 1460830 Hom.: 17604 Cov.: 32 AF XY: 0.150 AC XY: 108754 AN XY: 726804

African (AFR) AF: 0.279 AC: 9324 AN: 33424

American (AMR) AF: 0.130 AC: 5810 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 4392 AN: 26124

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39694

South Asian (SAS) AF: 0.120 AC: 10318 AN: 86238

European-Finnish (FIN) AF: 0.146 AC: 7811 AN: 53412

Middle Eastern (MID) AF: 0.160 AC: 920 AN: 5768

European-Non Finnish (NFE) AF: 0.155 AC: 172333 AN: 1111092

Other (OTH) AF: 0.150 AC: 9033 AN: 60360

GnomAD4 genome AF: 0.180 AC: 27418 AN: 152048 Hom.: 2779 Cov.: 32 AF XY: 0.177 AC XY: 13162 AN XY: 74356

African (AFR) AF: 0.272 AC: 11253 AN: 41432

American (AMR) AF: 0.142 AC: 2168 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 569 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5188

South Asian (SAS) AF: 0.105 AC: 508 AN: 4824

European-Finnish (FIN) AF: 0.146 AC: 1546 AN: 10572

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10725 AN: 67966

Other (OTH) AF: 0.190 AC: 400 AN: 2106

Alfa AF: 0.170 Hom.: 3578

Bravo AF: 0.185

Asia WGS AF: 0.0690 AC: 246 AN: 3478

EpiCase AF: 0.166

EpiControl AF: 0.172

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.82
DANN	Benign	0.64
PhyloP100		-0.69
Mutation Taster		=100/0	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: rs3184982; hg19: chr4-185615768; COSMIC: COSV55657724; COSMIC: COSV55657724;