Variant 4-184694537-ACAGATGAAG-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM4BP6BA1

The NM_152683.4(PRIMPOL):c.1450_1458delGCAGATGAA(p.Ala484_Glu486del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,613,116 control chromosomes in the GnomAD database, including 1,460 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.055 ( 745 hom., cov: 32)

Exomes 𝑓: 0.0060 ( 715 hom. )

Consequence

PRIMPOL
NM_152683.4 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.13

Variant links:

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]

PRIMPOL links:

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]

CENPU links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_152683.4.

BP6

Variant 4-184694537-ACAGATGAAG-A is Benign according to our data. Variant chr4-184694537-ACAGATGAAG-A is described in ClinVar as [Benign]. Clinvar id is 3056030.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRIMPOL	NM_152683.4 link	c.1450_1458delGCAGATGAA	p.Ala484_Glu486del	conservative_inframe_deletion	Exon 14 of 14	ENST00000314970.11	NP_689896.1	Q96LW4-1
CENPU	NM_024629.4 link	c.742_750delCTTCATCTG		3_prime_UTR_variant	Exon 13 of 13	ENST00000281453.10	NP_078905.2	Q71F23-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRIMPOL	ENST00000314970.11 link	c.1450_1458delGCAGATGAA	p.Ala484_Glu486del	conservative_inframe_deletion	Exon 14 of 14	1	NM_152683.4	ENSP00000313816.6		Q96LW4-1
CENPU	ENST00000281453 link	c.742_750delCTTCATCTG		3_prime_UTR_variant	Exon 13 of 13	1	NM_024629.4	ENSP00000281453.5		Q71F23-1

Frequencies

GnomAD3 genomes

AF:

0.0554

AC:

8424

AN:

152126

Hom.:

745

Cov.:

show subpopulations

Gnomad AFR

AF:

0.190

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0260

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000955

Gnomad OTH

AF:

0.0483

GnomAD3 exomes

AF:

0.0143

AC:

3583

AN:

250858

Hom.:

297

AF XY:

0.0110

AC XY:

1489

AN XY:

135672

show subpopulations

Gnomad AFR exome

AF:

0.191

Gnomad AMR exome

AF:

0.00936

Gnomad ASJ exome

AF:

0.00418

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000661

Gnomad OTH exome

AF:

0.00786

GnomAD4 exome

AF:

0.00600

AC:

8760

AN:

1460872

Hom.:

715

AF XY:

0.00516

AC XY:

3751

AN XY:

726604

show subpopulations

Gnomad4 AFR exome

AF:

0.200

Gnomad4 AMR exome

AF:

0.0110

Gnomad4 ASJ exome

AF:

0.00368

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000545

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000539

Gnomad4 OTH exome

AF:

0.0134

GnomAD4 genome

AF:

0.0555

AC:

8445

AN:

152244

Hom.:

745

Cov.:

AF XY:

0.0533

AC XY:

3971

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.190

Gnomad4 AMR

AF:

0.0259

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000955

Gnomad4 OTH

AF:

0.0478

Alfa

AF:

0.0328

Hom.:

Bravo

AF:

0.0626

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PRIMPOL-related disorder

Benign:1

Apr 26, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over