3-58384450-G-T

Variant names:

• chr3-58384450-G-T
• rs6445975
• NM_017771.5:c.388+1750G>T

Variant summary

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

The NM_017771.5(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 NM_017771.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.997
• Publications: 98 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 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.388+1750G>T		intron	N/A	NP_060241.2
	PXK	NM_001349492.2		c.388+1750G>T		intron	N/A	NP_001336421.1
	PXK	NM_001349493.2		c.388+1750G>T		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.388+1750G>T		intron	N/A	ENSP00000348472.2	Q7Z7A4-1
	PXK	ENST00000302779.9	TSL:1	c.388+1750G>T		intron	N/A	ENSP00000305045.6	W5RWE6
	PXK	ENST00000383716.7	TSL:1	c.388+1750G>T		intron	N/A	ENSP00000373222.4	Q7Z7A4-2

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

African (AFR) AF: 0.446 AC: 18443 AN: 41372

American (AMR) AF: 0.680 AC: 10392 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 2717 AN: 3470

East Asian (EAS) AF: 0.806 AC: 4184 AN: 5190

South Asian (SAS) AF: 0.757 AC: 3648 AN: 4818

European-Finnish (FIN) AF: 0.648 AC: 6833 AN: 10552

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.707 AC: 48076 AN: 67988

Other (OTH) AF: 0.693 AC: 1464 AN: 2112

Alfa AF: 0.694 Hom.: 172876

Bravo AF: 0.624

Asia WGS AF: 0.740 AC: 2573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.53
DANN	Benign	0.67
PhyloP100		-1.0
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: rs6445975; hg19: chr3-58370177;