rs375318244

Variant names:

• chr3-58382520-G-A
• rs375318244
• NM_017771.5:c.208G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.21
• Publications: 1 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19643462).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017771.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PXK	NM_017771.5	MANE Select	c.208G>A	p.Gly70Ser	missense	Exon 4 of 18	NP_060241.2
	PXK	NM_001349492.2		c.208G>A	p.Gly70Ser	missense	Exon 4 of 19	NP_001336421.1
	PXK	NM_001349493.2		c.208G>A	p.Gly70Ser	missense	Exon 4 of 19	NP_001336422.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PXK	ENST00000356151.7	TSL:1 MANE Select	c.208G>A	p.Gly70Ser	missense	Exon 4 of 18	ENSP00000348472.2	Q7Z7A4-1
	PXK	ENST00000302779.9	TSL:1	c.208G>A	p.Gly70Ser	missense	Exon 4 of 17	ENSP00000305045.6	W5RWE6
	PXK	ENST00000383716.7	TSL:1	c.208G>A	p.Gly70Ser	missense	Exon 4 of 19	ENSP00000373222.4	Q7Z7A4-2

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 27 AN: 147126 Hom.: 0 Cov.: 31

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

GnomAD2 exomes AF: 0.000176 AC: 35 AN: 198614 AF XY: 0.000156

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 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.: 1 Cov.: 35 AF XY: 0.000158 AC XY: 109 AN XY: 692014

African (AFR) AF: 0.0000339 AC: 1 AN: 29520

American (AMR) AF: 0.00 AC: 0 AN: 29772

Ashkenazi Jewish (ASJ) AF: 0.000767 AC: 18 AN: 23478

East Asian (EAS) AF: 0.00 AC: 0 AN: 37264

South Asian (SAS) AF: 0.00 AC: 0 AN: 75476

European-Finnish (FIN) AF: 0.0000590 AC: 3 AN: 50822

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5088

European-Non Finnish (NFE) AF: 0.000158 AC: 171 AN: 1083676

Other (OTH) AF: 0.000192 AC: 11 AN: 57262

GnomAD4 genome AF: 0.000184 AC: 27 AN: 147126 Hom.: 0 Cov.: 31 AF XY: 0.0000984 AC XY: 7 AN XY: 71120

African (AFR) AF: 0.00 AC: 0 AN: 39854

American (AMR) AF: 0.0000684 AC: 1 AN: 14618

Ashkenazi Jewish (ASJ) AF: 0.000869 AC: 3 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5048

South Asian (SAS) AF: 0.00 AC: 0 AN: 4700

European-Finnish (FIN) AF: 0.000224 AC: 2 AN: 8944

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 298

European-Non Finnish (NFE) AF: 0.000312 AC: 21 AN: 67304

Other (OTH) AF: 0.00 AC: 0 AN: 2004

Alfa AF: 0.000253 Hom.: 0

Bravo AF: 0.000159

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000148 AC: 18

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.067	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		6.2
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.17
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.033	D
Polyphen		0.54	P
Vest4		0.26
MVP		0.56
MPC		0.30
ClinPred		0.30	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.38
gMVP		0.44
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

dbSNP: rs375318244; hg19: chr3-58368247;