rs4681851

Variant names:

• chr3-58410164-C-G
• rs4681851
• NM_017771.5:c.1465+5C>G

Variant summary

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

The NM_017771.5(PXK):​c.1465+5C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,569,252 control chromosomes in the GnomAD database, including 18,683 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (1602 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17081 hom.)
• Consequence: PXK NM_017771.5 splice_region, intron
• Scores: Splicing: ADA: 0.0002148
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.431
• Publications: 23 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=-0.5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017771.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PXK	NM_017771.5	MANE Select	c.1465+5C>G		splice_region intron	N/A	NP_060241.2
	PXK	NM_001349492.2		c.1465+5C>G		splice_region intron	N/A	NP_001336421.1
	PXK	NM_001349493.2		c.1465+5C>G		splice_region intron	N/A	NP_001336422.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PXK	ENST00000356151.7	TSL:1 MANE Select	c.1465+5C>G		splice_region intron	N/A	ENSP00000348472.2	Q7Z7A4-1
	PXK	ENST00000302779.9	TSL:1	c.1465+5C>G		splice_region intron	N/A	ENSP00000305045.6	W5RWE6
	PXK	ENST00000383716.7	TSL:1	c.1465+5C>G		splice_region intron	N/A	ENSP00000373222.4	Q7Z7A4-2

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22146 AN: 151956 Hom.: 1600 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.140

GnomAD2 exomes AF: 0.154 AC: 38789 AN: 251128 AF XY: 0.151

Gnomad AFR exome AF: 0.138

Gnomad AMR exome AF: 0.187

Gnomad ASJ exome AF: 0.118

Gnomad EAS exome AF: 0.182

Gnomad FIN exome AF: 0.160

Gnomad NFE exome AF: 0.146

Gnomad OTH exome AF: 0.155

GnomAD4 exome AF: 0.153 AC: 217520 AN: 1417178 Hom.: 17081 Cov.: 29 AF XY: 0.153 AC XY: 108272 AN XY: 707290

African (AFR) AF: 0.132 AC: 4310 AN: 32622

American (AMR) AF: 0.181 AC: 8100 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 3083 AN: 25870

East Asian (EAS) AF: 0.209 AC: 8278 AN: 39562

South Asian (SAS) AF: 0.147 AC: 12544 AN: 85386

European-Finnish (FIN) AF: 0.164 AC: 8724 AN: 53280

Middle Eastern (MID) AF: 0.140 AC: 794 AN: 5674

European-Non Finnish (NFE) AF: 0.152 AC: 162593 AN: 1071154

Other (OTH) AF: 0.154 AC: 9094 AN: 58990

GnomAD4 genome AF: 0.146 AC: 22168 AN: 152074 Hom.: 1602 Cov.: 32 AF XY: 0.147 AC XY: 10910 AN XY: 74350

African (AFR) AF: 0.136 AC: 5632 AN: 41464

American (AMR) AF: 0.148 AC: 2261 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 421 AN: 3462

East Asian (EAS) AF: 0.191 AC: 987 AN: 5170

South Asian (SAS) AF: 0.136 AC: 656 AN: 4826

European-Finnish (FIN) AF: 0.165 AC: 1739 AN: 10560

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10046 AN: 67998

Other (OTH) AF: 0.140 AC: 297 AN: 2116

Alfa AF: 0.145 Hom.: 491

Bravo AF: 0.148

Asia WGS AF: 0.174 AC: 604 AN: 3478

EpiCase AF: 0.141

EpiControl AF: 0.143

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Benign	0.71
PhyloP100		0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00021
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.010		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: rs4681851; hg19: chr3-58395891;