rs751989239

Variant names:

• chr3-58382548-A-G
• rs751989239
• NM_017771.5:c.236A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017771.5(PXK):​c.236A>G​(p.Lys79Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000529 in 1,437,532 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000053 (0 hom.)
• Consequence: PXK NM_017771.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.68
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.236A>G	p.Lys79Arg	missense	Exon 4 of 18	NP_060241.2
	PXK	NM_001349492.2		c.236A>G	p.Lys79Arg	missense	Exon 4 of 19	NP_001336421.1
	PXK	NM_001349493.2		c.236A>G	p.Lys79Arg	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.236A>G	p.Lys79Arg	missense	Exon 4 of 18	ENSP00000348472.2	Q7Z7A4-1
	PXK	ENST00000302779.9	TSL:1	c.236A>G	p.Lys79Arg	missense	Exon 4 of 17	ENSP00000305045.6	W5RWE6
	PXK	ENST00000383716.7	TSL:1	c.236A>G	p.Lys79Arg	missense	Exon 4 of 19	ENSP00000373222.4	Q7Z7A4-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000440 AC: 1 AN: 227020 AF XY: 0.00000812

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000940

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000529 AC: 76 AN: 1437532 Hom.: 0 Cov.: 35 AF XY: 0.0000560 AC XY: 40 AN XY: 714716

African (AFR) AF: 0.0000313 AC: 1 AN: 31964

American (AMR) AF: 0.00 AC: 0 AN: 38640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25256

East Asian (EAS) AF: 0.00 AC: 0 AN: 38674

South Asian (SAS) AF: 0.00 AC: 0 AN: 80812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 0.0000643 AC: 71 AN: 1104200

Other (OTH) AF: 0.0000674 AC: 4 AN: 59336

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000624 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

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	0.33
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.81	L
PhyloP100		8.7
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.22
Sift	Benign	0.28	T
Sift4G	Benign	0.13	T
Polyphen		1.0	D
Vest4		0.55
MutPred		0.62		Loss of glycosylation at P77 (P = 0.0042)
MVP		0.75
MPC		0.52
ClinPred		0.84	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.20
gMVP		0.37
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs751989239; hg19: chr3-58368275;