rs6772228

Variant names:

• chr3-58390292-T-A
• rs6772228
• NM_017771.5:c.389-290T>A

Variant summary

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

The NM_017771.5(PXK):​c.389-290T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0303 in 152,252 control chromosomes in the GnomAD database, including 104 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 0.030 (104 hom., cov: 31)
• Consequence: PXK NM_017771.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0750
• Publications: 38 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=-0.62).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0501 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.389-290T>A		intron	N/A	NP_060241.2
	PXK	NM_001349492.2		c.389-290T>A		intron	N/A	NP_001336421.1
	PXK	NM_001349493.2		c.389-290T>A		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.389-290T>A		intron	N/A	ENSP00000348472.2	Q7Z7A4-1
	PXK	ENST00000302779.9	TSL:1	c.389-290T>A		intron	N/A	ENSP00000305045.6	W5RWE6
	PXK	ENST00000383716.7	TSL:1	c.389-290T>A		intron	N/A	ENSP00000373222.4	Q7Z7A4-2

Frequencies

GnomAD3 genomes AF: 0.0304 AC: 4618 AN: 152134 Hom.: 104 Cov.: 31

Gnomad AFR AF: 0.00953

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0183

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0130

Gnomad FIN AF: 0.0235

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0515

Gnomad OTH AF: 0.0225

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

GnomAD4 genome AF: 0.0303 AC: 4618 AN: 152252 Hom.: 104 Cov.: 31 AF XY: 0.0287 AC XY: 2134 AN XY: 74430

African (AFR) AF: 0.00951 AC: 395 AN: 41552

American (AMR) AF: 0.0182 AC: 279 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 70 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.0131 AC: 63 AN: 4826

European-Finnish (FIN) AF: 0.0235 AC: 249 AN: 10588

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0515 AC: 3505 AN: 68016

Other (OTH) AF: 0.0222 AC: 47 AN: 2114

Alfa AF: 0.0417 Hom.: 15

Bravo AF: 0.0295

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	8.0
DANN	Benign	0.90
PhyloP100		-0.075
Mutation Taster		=100/0	polymorphism

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: rs6772228; hg19: chr3-58376019;