Variant 3-58397708-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017771.5(PXK):c.1088C>T(p.Pro363Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000806 in 1,613,498 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

PXK
NM_017771.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.36

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19605684).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PXK	NM_017771.5 linkuse as main transcript	c.1088C>T	p.Pro363Leu	missense_variant	11/18	ENST00000356151.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PXK	ENST00000356151.7 linkuse as main transcript	c.1088C>T	p.Pro363Leu	missense_variant	11/18	1	NM_017771.5	P1	Q7Z7A4-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251180

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135728

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461240

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

726956

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 16, 2024

The c.1088C>T (p.P363L) alteration is located in exon 11 (coding exon 11) of the PXK gene. This alteration results from a C to T substitution at nucleotide position 1088, causing the proline (P) at amino acid position 363 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

T;T;.;.;.;.;T;T

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.91

D;D;D;D;D;.;D;D

M_CAP

Benign

0.017

MetaRNN

Benign

0.20

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.56

MutationAssessor

Benign

1.5

L;.;L;.;.;L;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-2.2

N;.;.;N;N;N;N;.

REVEL

Benign

0.14

Sift

Benign

0.10

T;.;.;T;T;T;T;.

Sift4G

Benign

0.36

T;T;T;T;T;T;T;D

Polyphen

0.0060

B;.;B;P;.;B;.;.

Vest4

0.75

MVP

0.26

MPC

0.29

ClinPred

0.53

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.096

gMVP

0.61

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over