rs2176082

Positions:

• chr3-58345459-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.102+12369G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,000 control chromosomes in the GnomAD database, including 10,592 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 0.36 (10592 hom., cov: 32)
• Consequence: PXK NM_017771.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PXK	NM_017771.5	c.102+12369G>A		intron_variant		ENST00000356151.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PXK	ENST00000356151.7	c.102+12369G>A		intron_variant		1	NM_017771.5	P1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53993 AN: 151882 Hom.: 10578 Cov.: 32

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.302

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.356 AC: 54057 AN: 152000 Hom.: 10592 Cov.: 32 AF XY: 0.354 AC XY: 26313 AN XY: 74302

Gnomad4 AFR AF: 0.524

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.300

Alfa AF: 0.296 Hom.: 7742

Bravo AF: 0.365

Asia WGS AF: 0.251 AC: 873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.79

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: rs2176082; hg19: chr3-58331186;