Variant 3-58382520-G-A 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.208G>A(p.Gly70Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00015 in 1,539,484 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

PXK
NM_017771.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.21

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=0.19643462).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PXK	NM_017771.5 linkuse as main transcript	c.208G>A	p.Gly70Ser	missense_variant	4/18	ENST00000356151.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PXK	ENST00000356151.7 linkuse as main transcript	c.208G>A	p.Gly70Ser	missense_variant	4/18	1	NM_017771.5	P1	Q7Z7A4-1

Frequencies

GnomAD3 genomes

AF:

0.000184

AC:

AN:

147126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000684

Gnomad ASJ

AF:

0.000869

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000224

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000312

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000176

AC:

AN:

198614

Hom.:

AF XY:

0.000156

AC XY:

AN XY:

109076

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000401

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000521

Gnomad NFE exome

AF:

0.000308

Gnomad OTH exome

AF:

0.000229

GnomAD4 exome

AF:

0.000147

AC:

204

AN:

1392358

Hom.:

Cov.:

AF XY:

0.000158

AC XY:

109

AN XY:

692014

show subpopulations

Gnomad4 AFR exome

AF:

0.0000339

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000767

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000590

Gnomad4 NFE exome

AF:

0.000158

Gnomad4 OTH exome

AF:

0.000192

GnomAD4 genome

AF:

0.000184

AC:

AN:

147126

Hom.:

Cov.:

AF XY:

0.0000984

AC XY:

AN XY:

71120

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000684

Gnomad4 ASJ

AF:

0.000869

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000224

Gnomad4 NFE

AF:

0.000312

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000253

Hom.:

Bravo

AF:

0.000159

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000148

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

Mar 22, 2022

The c.208G>A (p.G70S) alteration is located in exon 4 (coding exon 4) of the PXK gene. This alteration results from a G to A substitution at nucleotide position 208, causing the glycine (G) at amino acid position 70 to be replaced by a serine (S). 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

0.085

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.067

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

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.93

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

M_CAP

Benign

0.0097

MetaRNN

Benign

0.20

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

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;.;M;.;.;M;.;.

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-4.2

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

REVEL

Benign

0.17

Sift

Uncertain

0.015

D;.;.;D;D;D;T;T

Sift4G

Uncertain

0.033

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

Polyphen

0.54

P;.;P;P;.;P;.;.

Vest4

0.26

MVP

0.56

MPC

0.30

ClinPred

0.30

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.38

gMVP

0.44

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