4-184694537-ACAGATGAAG-ACAGATGAAGCAGATGAAG

Variant names:

• chr4-184694537-A-ACAGATGAAG
• NM_152683.4:c.1450_1458dupGCAGATGAA

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_152683.4(PRIMPOL):​c.1450_1458dupGCAGATGAA​(p.Ala484_Glu486dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRIMPOL NM_152683.4 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_152683.4.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRIMPOL	NM_152683.4	c.1450_1458dupGCAGATGAA	p.Ala484_Glu486dup	conservative_inframe_insertion	Exon 14 of 14	ENST00000314970.11	NP_689896.1
CENPU	NM_024629.4	c.*742_*750dupCTTCATCTG		3_prime_UTR_variant	Exon 13 of 13	ENST00000281453.10	NP_078905.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRIMPOL	ENST00000314970.11	c.1450_1458dupGCAGATGAA	p.Ala484_Glu486dup	conservative_inframe_insertion	Exon 14 of 14	1	NM_152683.4	ENSP00000313816.6
CENPU	ENST00000281453	c.*742_*750dupCTTCATCTG		3_prime_UTR_variant	Exon 13 of 13	1	NM_024629.4	ENSP00000281453.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-185615691;