rs112271283

Variant names:

• chr4-184659367-A-G
• rs112271283
• NM_152683.4:c.208A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_152683.4(PRIMPOL):​c.208A>G​(p.Lys70Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000075 in 1,613,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000074 (0 hom.)
• Consequence: PRIMPOL NM_152683.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.40
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008662492).
• BS2: High AC in GnomAd4 at 13 AD gene.

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.208A>G	p.Lys70Glu	missense	Exon 4 of 14	NP_689896.1	Q96LW4-1
	PRIMPOL	NM_001345891.2		c.208A>G	p.Lys70Glu	missense	Exon 4 of 15	NP_001332820.1
	PRIMPOL	NM_001345892.2		c.208A>G	p.Lys70Glu	missense	Exon 4 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.208A>G	p.Lys70Glu	missense	Exon 4 of 14	ENSP00000313816.6	Q96LW4-1
	PRIMPOL	ENST00000512834.5	TSL:1	c.208A>G	p.Lys70Glu	missense	Exon 4 of 14	ENSP00000425316.1	Q96LW4-2
	PRIMPOL	ENST00000515774.5	TSL:1	c.-180A>G		5_prime_UTR	Exon 3 of 13	ENSP00000421913.1	A0A5S6SZ32

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152218 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000239 AC: 60 AN: 251242 AF XY: 0.000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00122

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000616

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.0000739 AC: 108 AN: 1461534 Hom.: 0 Cov.: 30 AF XY: 0.0000743 AC XY: 54 AN XY: 727078

African (AFR) AF: 0.0000896 AC: 3 AN: 33476

American (AMR) AF: 0.00121 AC: 54 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000868 AC: 5 AN: 5762

European-Non Finnish (NFE) AF: 0.0000279 AC: 31 AN: 1111800

Other (OTH) AF: 0.000232 AC: 14 AN: 60378

GnomAD4 genome AF: 0.0000853 AC: 13 AN: 152336 Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8 AN XY: 74486

African (AFR) AF: 0.0000481 AC: 2 AN: 41578

American (AMR) AF: 0.000392 AC: 6 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000700 Hom.: 0

Bravo AF: 0.000125

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000395 AC: 48

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.00042	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.0087	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.4
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.63	N
REVEL	Benign	0.088
Sift	Benign	0.71	T
Sift4G	Benign	0.94	T
Polyphen		0.93	P
Vest4		0.14
MVP		0.24
MPC		0.063
ClinPred		0.093	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.41
Mutation Taster		=73/27	polymorphism

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: rs112271283; hg19: chr4-185580521;