dbSNP rs6767498: PXK:c.1529-1353C>A (chr3-58423399-C-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_001349492.2(PXK):c.1529-62C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 1,508,952 control chromosomes in the GnomAD database, including 206,295 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 0.50 ( 19930 hom., cov: 33)

Exomes 𝑓: 0.51 ( 186365 hom. )

Consequence

PXK
NM_001349492.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.97

Publications

15 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=-0.78).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349492.2. 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.1529-1353C>A	intron	N/A	NP_060241.2
PXK	NM_001349492.2		c.1529-62C>A	intron	N/A	NP_001336421.1
PXK	NM_001349493.2		c.1526-62C>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.1529-1353C>A	intron	N/A	ENSP00000348472.2
PXK	ENST00000302779.9	TSL:1	c.1466-1353C>A	intron	N/A	ENSP00000305045.6
PXK	ENST00000383716.7	TSL:1	c.*14-1353C>A	intron	N/A	ENSP00000373222.4

Frequencies

GnomAD3 genomes

AF:

0.499

AC:

75839

AN:

151924

Hom.:

19914

Cov.:

show subpopulations

Gnomad AFR

AF:

0.535

Gnomad AMI

AF:

0.493

Gnomad AMR

AF:

0.448

Gnomad ASJ

AF:

0.668

Gnomad EAS

AF:

0.00404

Gnomad SAS

AF:

0.363

Gnomad FIN

AF:

0.421

Gnomad MID

AF:

0.573

Gnomad NFE

AF:

0.539

Gnomad OTH

AF:

0.517

GnomAD4 exome

AF:

0.514

AC:

697047

AN:

1356910

Hom.:

186365

Cov.:

AF XY:

0.511

AC XY:

342905

AN XY:

670810

show subpopulations

African (AFR)

AF:

0.536

AC:

16612

AN:

30996

American (AMR)

AF:

0.396

AC:

14082

AN:

35590

Ashkenazi Jewish (ASJ)

AF:

0.665

AC:

16621

AN:

24976

East Asian (EAS)

AF:

0.00213

AC:

AN:

35618

South Asian (SAS)

AF:

0.404

AC:

31754

AN:

78592

European-Finnish (FIN)

AF:

0.410

AC:

13876

AN:

33872

Middle Eastern (MID)

AF:

0.582

AC:

3278

AN:

5634

European-Non Finnish (NFE)

AF:

0.543

AC:

572175

AN:

1054548

Other (OTH)

AF:

0.501

AC:

28573

AN:

57084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

17005

34010

51014

68019

85024

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16164

32328

48492

64656

80820

<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:

0.499

AC:

75888

AN:

152042

Hom.:

19930

Cov.:

AF XY:

0.488

AC XY:

36274

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.535

AC:

22183

AN:

41430

American (AMR)

AF:

0.447

AC:

6831

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.668

AC:

2317

AN:

3470

East Asian (EAS)

AF:

0.00425

AC:

AN:

5182

South Asian (SAS)

AF:

0.364

AC:

1751

AN:

4816

European-Finnish (FIN)

AF:

0.421

AC:

4439

AN:

10550

Middle Eastern (MID)

AF:

0.565

AC:

165

AN:

292

European-Non Finnish (NFE)

AF:

0.539

AC:

36652

AN:

67988

Other (OTH)

AF:

0.510

AC:

1078

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1929

3858

5788

7717

9646

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

668

1336

2004

2672

3340

<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:

0.527

Hom.:

16248

Bravo

AF:

0.502

Asia WGS

AF:

0.193

AC:

675

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.1

(source)

DANN

Benign

0.80

PhyloP100

-2.0

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