3-58384450-G-T

Position:

• chr3-58384450-G-T

Variant summary

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

The ENST00000356151.7(PXK):​c.388+1750G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 151,996 control chromosomes in the GnomAD database, including 31,940 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 0.64 (31940 hom., cov: 32)
• Consequence: PXK ENST00000356151.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.997

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PXK	NM_017771.5	c.388+1750G>T		intron_variant		ENST00000356151.7	NP_060241.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PXK	ENST00000356151.7	c.388+1750G>T		intron_variant		1	NM_017771.5	ENSP00000348472	P1

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96650 AN: 151878 Hom.: 31932 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.802

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.692

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

GnomAD4 genome AF: 0.636 AC: 96696 AN: 151996 Hom.: 31940 Cov.: 32 AF XY: 0.638 AC XY: 47402 AN XY: 74300

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.680

Gnomad4 ASJ AF: 0.783

Gnomad4 EAS AF: 0.806

Gnomad4 SAS AF: 0.757

Gnomad4 FIN AF: 0.648

Gnomad4 NFE AF: 0.707

Gnomad4 OTH AF: 0.693

Alfa AF: 0.709 Hom.: 88762

Bravo AF: 0.624

Asia WGS AF: 0.740 AC: 2573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.53
DANN	Benign	0.67

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: rs6445975; hg19: chr3-58370177;