Variant 3-58403905-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_017771.5(PXK):c.1225T>G(p.Phe409Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000411 in 1,531,598 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00040 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PXK
NM_017771.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.40

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00822553).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PXK	NM_017771.5 linkuse as main transcript	c.1225T>G	p.Phe409Val	missense_variant	13/18	ENST00000356151.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PXK	ENST00000356151.7 linkuse as main transcript	c.1225T>G	p.Phe409Val	missense_variant	13/18	1	NM_017771.5	P1	Q7Z7A4-1

Frequencies

GnomAD3 genomes

AF:

0.000401

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000417

AC:

AN:

239534

Hom.:

AF XY:

0.00000771

AC XY:

AN XY:

129690

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000900

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000145

AC:

AN:

1379390

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

680354

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000189

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000401

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000499

ExAC

AF:

0.00000824

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

Apr 25, 2023

The c.1225T>G (p.F409V) alteration is located in exon 13 (coding exon 13) of the PXK gene. This alteration results from a T to G substitution at nucleotide position 1225, causing the phenylalanine (F) at amino acid position 409 to be replaced by a valine (V). 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

Uncertain

0.47

BayesDel_addAF

Uncertain

0.089

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Benign

0.93

DEOGEN2

Benign

0.014

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

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.94

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

M_CAP

Benign

0.038

MetaRNN

Benign

0.0082

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

MetaSVM

Benign

-0.60

MutationAssessor

Benign

0.95

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

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-2.1

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

REVEL

Benign

0.13

Sift

Uncertain

0.0090

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

Sift4G

Benign

0.10

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

Polyphen

0.030

B;.;B;B;.;B;.;.

Vest4

0.47

MutPred

0.40

Gain of glycosylation at T413 (P = 0.025);Gain of glycosylation at T413 (P = 0.025);Gain of glycosylation at T413 (P = 0.025);.;.;Gain of glycosylation at T413 (P = 0.025);.;.;

MVP

0.68

MPC

0.39

ClinPred

0.33

GERP RS

5.7

Varity_R

0.18

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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