Genetic Variant PXK:c.721-98G>A (chr3-58395560-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017771.5(PXK):c.721-98G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0829 in 861,296 control chromosomes in the GnomAD database, including 3,472 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 0.074 ( 532 hom., cov: 32)

Exomes 𝑓: 0.085 ( 2940 hom. )

Consequence

PXK
NM_017771.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.33

Publications

49 publications found

Variant links:

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

PXK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0946 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PXK	NM_017771.5	MANE Select	c.721-98G>A	intron	N/A	NP_060241.2
PXK	NM_001349492.2		c.721-98G>A	intron	N/A	NP_001336421.1
PXK	NM_001349493.2		c.721-98G>A	intron	N/A	NP_001336422.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PXK	ENST00000356151.7	TSL:1 MANE Select	c.721-98G>A	intron	N/A	ENSP00000348472.2
PXK	ENST00000302779.9	TSL:1	c.721-98G>A	intron	N/A	ENSP00000305045.6
PXK	ENST00000383716.7	TSL:1	c.721-98G>A	intron	N/A	ENSP00000373222.4

Frequencies

GnomAD3 genomes

AF:

0.0741

AC:

11269

AN:

152108

Hom.:

533

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0538

Gnomad AMI

AF:

0.0910

Gnomad AMR

AF:

0.0516

Gnomad ASJ

AF:

0.131

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.0952

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0885

Gnomad OTH

AF:

0.0740

GnomAD4 exome

AF:

0.0848

AC:

60129

AN:

709070

Hom.:

2940

AF XY:

0.0861

AC XY:

31922

AN XY:

370940

show subpopulations

African (AFR)

AF:

0.0508

AC:

856

AN:

16842

American (AMR)

AF:

0.0453

AC:

1159

AN:

25590

Ashkenazi Jewish (ASJ)

AF:

0.129

AC:

2171

AN:

16788

East Asian (EAS)

AF:

0.000669

AC:

AN:

34376

South Asian (SAS)

AF:

0.108

AC:

5926

AN:

55102

European-Finnish (FIN)

AF:

0.0913

AC:

4418

AN:

48392

Middle Eastern (MID)

AF:

0.137

AC:

554

AN:

4042

European-Non Finnish (NFE)

AF:

0.0890

AC:

42175

AN:

473886

Other (OTH)

AF:

0.0836

AC:

2847

AN:

34052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

2595

5189

7784

10378

12973

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

946

1892

2838

3784

4730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0740

AC:

11259

AN:

152226

Hom.:

532

Cov.:

AF XY:

0.0741

AC XY:

5516

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0536

AC:

2227

AN:

41522

American (AMR)

AF:

0.0515

AC:

787

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.131

AC:

454

AN:

3472

East Asian (EAS)

AF:

0.00135

AC:

AN:

5184

South Asian (SAS)

AF:

0.102

AC:

492

AN:

4820

European-Finnish (FIN)

AF:

0.0952

AC:

1009

AN:

10604

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0885

AC:

6021

AN:

68010

Other (OTH)

AF:

0.0723

AC:

153

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

531

1061

1592

2122

2653

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0837

Hom.:

1709

Bravo

AF:

0.0681

Asia WGS

AF:

0.0420

AC:

145

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.29

(source)

DANN

Benign

0.68

PhyloP100

-1.3

PromoterAI

0.0083

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over