3-58395560-G-A

Position:

• chr3-58395560-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PXK	NM_017771.5	c.721-98G>A		intron_variant		ENST00000356151.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PXK	ENST00000356151.7	c.721-98G>A		intron_variant		1	NM_017771.5	P1

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

Gnomad4 AFR exome AF: 0.0508

Gnomad4 AMR exome AF: 0.0453

Gnomad4 ASJ exome AF: 0.129

Gnomad4 EAS exome AF: 0.000669

Gnomad4 SAS exome AF: 0.108

Gnomad4 FIN exome AF: 0.0913

Gnomad4 NFE exome AF: 0.0890

Gnomad4 OTH exome AF: 0.0836

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

Gnomad4 AFR AF: 0.0536

Gnomad4 AMR AF: 0.0515

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0952

Gnomad4 NFE AF: 0.0885

Gnomad4 OTH AF: 0.0723

Alfa AF: 0.0871 Hom.: 699

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs13315871; hg19: chr3-58381287;