rs11711261

Positions:

• chr3-58357969-C-A
• chr3-58357969-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.103-7905C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 150,366 control chromosomes in the GnomAD database, including 4,759 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 0.22 (4759 hom., cov: 31)
• Consequence: PXK NM_017771.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.879

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PXK	NM_017771.5	c.103-7905C>A		intron_variant		ENST00000356151.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PXK	ENST00000356151.7	c.103-7905C>A		intron_variant		1	NM_017771.5	P1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33251 AN: 150262 Hom.: 4738 Cov.: 31

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.00156

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.221 AC: 33303 AN: 150366 Hom.: 4759 Cov.: 31 AF XY: 0.220 AC XY: 16151 AN XY: 73378

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.00156

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.186

Alfa AF: 0.0501 Hom.: 72

Bravo AF: 0.228

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.41
DANN	Benign	0.27

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: rs11711261; hg19: chr3-58343696;