rs3184982

chr4-184694614-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_152683.4(PRIMPOL):c.1518T>G(p.Gly506=) 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRIMPOL	NM_152683.4	c.1518T>G	p.Gly506=	synonymous_variant	14/14	ENST00000314970.11
CENPU	NM_024629.4	c.*674A>C		3_prime_UTR_variant	13/13	ENST00000281453.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRIMPOL	ENST00000314970.11	c.1518T>G	p.Gly506=	synonymous_variant	14/14	1	NM_152683.4	P4
CENPU	ENST00000281453.10	c.*674A>C		3_prime_UTR_variant	13/13	1	NM_024629.4	P1

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

GnomAD3 exomes AF: 0.144 AC: 36018 AN: 250094 Hom.: 2971 AF XY: 0.144 AC XY: 19513 AN XY: 135308

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 SAS exome AF: 0.118

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

Gnomad4 AFR exome AF: 0.279

Gnomad4 AMR exome AF: 0.130

Gnomad4 ASJ exome AF: 0.168

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.146

Gnomad4 NFE exome AF: 0.155

Gnomad4 OTH exome AF: 0.150

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

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.190

Alfa AF: 0.168 Hom.: 2786

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.82
Dann	Benign	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

Other links and lift over

dbSNP: rs3184982; hg19: chr4-185615768; COSMIC: COSV55657724; COSMIC: COSV55657724;