rs4681851

Positions:

• chr3-58410164-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017771.5(PXK):​c.1465+5C>G variant causes a splice donor 5th base, 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_donor_5th_base, intron
• Scores: Splicing: ADA: 0.0002148
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.431

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=-0.5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PXK	NM_017771.5	c.1465+5C>G		splice_donor_5th_base_variant, intron_variant		ENST00000356151.7	NP_060241.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PXK	ENST00000356151.7	c.1465+5C>G		splice_donor_5th_base_variant, intron_variant		1	NM_017771.5	ENSP00000348472	P1

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

GnomAD3 exomes AF: 0.154 AC: 38789 AN: 251128 Hom.: 3097 AF XY: 0.151 AC XY: 20499 AN XY: 135754

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 SAS exome AF: 0.148

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

Gnomad4 AFR exome AF: 0.132

Gnomad4 AMR exome AF: 0.181

Gnomad4 ASJ exome AF: 0.119

Gnomad4 EAS exome AF: 0.209

Gnomad4 SAS exome AF: 0.147

Gnomad4 FIN exome AF: 0.164

Gnomad4 NFE exome AF: 0.152

Gnomad4 OTH exome AF: 0.154

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

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.140

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs4681851; hg19: chr3-58395891;