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GeneBe

3-58391211-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_017771.5(PXK):c.531G>A(p.Val177=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,612,804 control chromosomes in the GnomAD database, including 149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0085 ( 8 hom., cov: 33)
Exomes 𝑓: 0.012 ( 141 hom. )

Consequence

PXK
NM_017771.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.825
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-58391211-G-A is Benign according to our data. Variant chr3-58391211-G-A is described in ClinVar as [Benign]. Clinvar id is 3024767.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.825 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PXKNM_017771.5 linkuse as main transcriptc.531G>A p.Val177= synonymous_variant 6/18 ENST00000356151.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PXKENST00000356151.7 linkuse as main transcriptc.531G>A p.Val177= synonymous_variant 6/181 NM_017771.5 P1Q7Z7A4-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00847
AC:
1290
AN:
152228
Hom.:
8
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00232
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00811
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00414
Gnomad FIN
AF:
0.00706
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0141
Gnomad OTH
AF:
0.00669
GnomAD3 exomes
AF:
0.00886
AC:
2227
AN:
251216
Hom.:
26
AF XY:
0.00921
AC XY:
1251
AN XY:
135772
show subpopulations
Gnomad AFR exome
AF:
0.00228
Gnomad AMR exome
AF:
0.00527
Gnomad ASJ exome
AF:
0.000198
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00360
Gnomad FIN exome
AF:
0.0102
Gnomad NFE exome
AF:
0.0142
Gnomad OTH exome
AF:
0.00979
GnomAD4 exome
AF:
0.0120
AC:
17487
AN:
1460458
Hom.:
141
Cov.:
30
AF XY:
0.0119
AC XY:
8630
AN XY:
726590
show subpopulations
Gnomad4 AFR exome
AF:
0.00200
Gnomad4 AMR exome
AF:
0.00524
Gnomad4 ASJ exome
AF:
0.000306
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00392
Gnomad4 FIN exome
AF:
0.0106
Gnomad4 NFE exome
AF:
0.0141
Gnomad4 OTH exome
AF:
0.00976
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00847
AC:
1290
AN:
152346
Hom.:
8
Cov.:
33
AF XY:
0.00780
AC XY:
581
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.00231
Gnomad4 AMR
AF:
0.00810
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00414
Gnomad4 FIN
AF:
0.00706
Gnomad4 NFE
AF:
0.0141
Gnomad4 OTH
AF:
0.00662
Alfa
AF:
0.0111
Hom.:
1
Bravo
AF:
0.00775
Asia WGS
AF:
0.000578
AC:
2
AN:
3476
EpiCase
AF:
0.0129
EpiControl
AF:
0.0126

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenFeb 01, 2024PXK: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.45
Cadd
Benign
5.3
Dann
Benign
0.77
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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.

Other links and lift over

dbSNP: rs55962533; hg19: chr3-58376938; COSMIC: COSV100243810; COSMIC: COSV100243810; API