rs13315871

Variant names:

• chr3-58395560-G-A
• rs13315871
• NM_017771.5:c.721-98G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-58395560-G-A
• chr3-58395560-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017771.5(PXK):​c.721-98G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0829 in 861,296 control chromosomes in the GnomAD database, including 3,472 homozygotes. 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: 𝑓 0.074 (532 hom., cov: 32)
  • Exomes 𝑓: 0.085 (2940 hom.)
• Consequence: PXK NM_017771.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 49 publications found

Genes affected

PXK (HGNC:23326): (PX domain containing serine/threonine kinase like) This gene encodes a phox (PX) domain-containing protein which may be involved in synaptic transmission and the ligand-induced internalization and degradation of epidermal growth factors. Variations in this gene may be associated with susceptibility to systemic lupus erythematosus (SLE). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

PXK Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PXK	NM_017771.5	c.721-98G>A		intron_variant	Intron 8 of 17	ENST00000356151.7	NP_060241.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PXK	ENST00000356151.7	c.721-98G>A		intron_variant	Intron 8 of 17	1	NM_017771.5	ENSP00000348472.2

Frequencies

GnomAD3 genomes AF: 0.0741 AC: 11269 AN: 152108 Hom.: 533 Cov.: 32

Gnomad AFR AF: 0.0538

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.0516

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0952

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0885

Gnomad OTH AF: 0.0740

GnomAD4 exome AF: 0.0848 AC: 60129 AN: 709070 Hom.: 2940 AF XY: 0.0861 AC XY: 31922 AN XY: 370940

African (AFR) AF: 0.0508 AC: 856 AN: 16842

American (AMR) AF: 0.0453 AC: 1159 AN: 25590

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 2171 AN: 16788

East Asian (EAS) AF: 0.000669 AC: 23 AN: 34376

South Asian (SAS) AF: 0.108 AC: 5926 AN: 55102

European-Finnish (FIN) AF: 0.0913 AC: 4418 AN: 48392

Middle Eastern (MID) AF: 0.137 AC: 554 AN: 4042

European-Non Finnish (NFE) AF: 0.0890 AC: 42175 AN: 473886

Other (OTH) AF: 0.0836 AC: 2847 AN: 34052

GnomAD4 genome AF: 0.0740 AC: 11259 AN: 152226 Hom.: 532 Cov.: 32 AF XY: 0.0741 AC XY: 5516 AN XY: 74436

African (AFR) AF: 0.0536 AC: 2227 AN: 41522

American (AMR) AF: 0.0515 AC: 787 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 454 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5184

South Asian (SAS) AF: 0.102 AC: 492 AN: 4820

European-Finnish (FIN) AF: 0.0952 AC: 1009 AN: 10604

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0885 AC: 6021 AN: 68010

Other (OTH) AF: 0.0723 AC: 153 AN: 2116

Alfa AF: 0.0837 Hom.: 1709

Bravo AF: 0.0681

Asia WGS AF: 0.0420 AC: 145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.29
DANN	Benign	0.68
PhyloP100		-1.3
PromoterAI		0.0083	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs13315871; hg19: chr3-58381287;