rs200857997

Variant names:

• chr4-184659424-T-A
• rs200857997
• NM_152683.4:c.265T>A

Your query was ambiguous. Multiple possible variants found:

• chr4-184659424-T-A
• chr4-184659424-T-C
• chr4-184659424-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152683.4(PRIMPOL):​c.265T>A​(p.Tyr89Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,524 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y89D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PRIMPOL NM_152683.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.54
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRIMPOL	NM_152683.4	c.265T>A	p.Tyr89Asn	missense_variant	Exon 4 of 14	ENST00000314970.11	NP_689896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRIMPOL	ENST00000314970.11	c.265T>A	p.Tyr89Asn	missense_variant	Exon 4 of 14	1	NM_152683.4	ENSP00000313816.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458524 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 725792

African (AFR) AF: 0.00 AC: 0 AN: 33390

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 86168

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1109022

Other (OTH) AF: 0.00 AC: 0 AN: 60266

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.060	T;T;.
Eigen	Benign	0.015
Eigen_PC	Benign	0.021
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.85	.;T;T
M_CAP	Benign	0.064	D
MetaRNN	Uncertain	0.55	D;D;D
MetaSVM	Benign	-1.1	T
PhyloP100		3.5
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.0	D;D;D
REVEL	Benign	0.16
Sift	Uncertain	0.014	D;D;D
Sift4G	Benign	0.13	T;T;D
Polyphen		0.96	D;D;.
Vest4		0.83
MutPred		0.41		Gain of methylation at K91 (P = 0.0712);Gain of methylation at K91 (P = 0.0712);Gain of methylation at K91 (P = 0.0712);
MVP		0.34
MPC		0.15
ClinPred		0.98	D
GERP RS		3.0
Varity_R		0.85
gMVP		0.77
Mutation Taster		=0/100	disease causing

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: rs200857997; hg19: chr4-185580578;