rs541152487

Variant names:

• chr4-184666010-C-A
• rs541152487
• NM_152683.4:c.502C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-184666010-C-A
• chr4-184666010-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_152683.4(PRIMPOL):​c.502C>A​(p.Arg168Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: PRIMPOL NM_152683.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.27
• Publications: 0 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]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.1).
• BP7: Synonymous conserved (PhyloP=2.27 with no splicing effect.

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.502C>A	p.Arg168Arg	synonymous	Exon 6 of 14	NP_689896.1	Q96LW4-1
	PRIMPOL	NM_001345891.2		c.502C>A	p.Arg168Arg	synonymous	Exon 6 of 15	NP_001332820.1
	PRIMPOL	NM_001345892.2		c.502C>A	p.Arg168Arg	synonymous	Exon 6 of 15	NP_001332821.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRIMPOL	ENST00000314970.11	TSL:1 MANE Select	c.502C>A	p.Arg168Arg	synonymous	Exon 6 of 14	ENSP00000313816.6	Q96LW4-1
	PRIMPOL	ENST00000512834.5	TSL:1	c.502C>A	p.Arg168Arg	synonymous	Exon 6 of 14	ENSP00000425316.1	Q96LW4-2
	PRIMPOL	ENST00000515774.5	TSL:1	c.115C>A	p.Arg39Arg	synonymous	Exon 5 of 13	ENSP00000421913.1	A0A5S6SZ32

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	8.6
DANN	Benign	0.97
PhyloP100		2.3

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: rs541152487; hg19: chr4-185587164;