rs2176082

Variant names:

• chr3-58345459-G-A
• rs2176082
• NM_017771.5:c.102+12369G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-58345459-G-A
• chr3-58345459-G-C
• chr3-58345459-G-T

Variant summary

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

The ENST00000356151.7(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 ENST00000356151.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155
• Publications: 35 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000356151.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PXK	NM_017771.5	MANE Select	c.102+12369G>A		intron	N/A	NP_060241.2
	PXK	NM_001349492.2		c.102+12369G>A		intron	N/A	NP_001336421.1
	PXK	NM_001349493.2		c.102+12369G>A		intron	N/A	NP_001336422.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PXK	ENST00000356151.7	TSL:1 MANE Select	c.102+12369G>A		intron	N/A	ENSP00000348472.2
	PXK	ENST00000302779.9	TSL:1	c.102+12369G>A		intron	N/A	ENSP00000305045.6
	PXK	ENST00000383716.7	TSL:1	c.102+12369G>A		intron	N/A	ENSP00000373222.4

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

African (AFR) AF: 0.524 AC: 21738 AN: 41446

American (AMR) AF: 0.315 AC: 4803 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 750 AN: 3466

East Asian (EAS) AF: 0.178 AC: 923 AN: 5186

South Asian (SAS) AF: 0.242 AC: 1164 AN: 4814

European-Finnish (FIN) AF: 0.353 AC: 3724 AN: 10544

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20059 AN: 67964

Other (OTH) AF: 0.300 AC: 632 AN: 2106

Alfa AF: 0.311 Hom.: 24218

Bravo AF: 0.365

Asia WGS AF: 0.251 AC: 873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.79
PhyloP100		-0.15
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: rs2176082; hg19: chr3-58331186;