rs143160176

Variant names:

• chr3-58399371-A-C
• NM_017771.5:c.1175A>C

Your query was ambiguous. Multiple possible variants found:

• chr3-58399371-A-C
• chr3-58399371-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017771.5(PXK):​c.1175A>C​(p.Gln392Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PXK NM_017771.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.70

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35799104).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PXK	NM_017771.5	c.1175A>C	p.Gln392Pro	missense_variant	Exon 12 of 18	ENST00000356151.7	NP_060241.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PXK	ENST00000356151.7	c.1175A>C	p.Gln392Pro	missense_variant	Exon 12 of 18	1	NM_017771.5	ENSP00000348472.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460160 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726544

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: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.070	T;T;.;.;.;.;T;T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D;D;D;D;D;.;D;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.36	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;.;M;.;.;M;.;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.8	N;.;.;N;N;N;N;.
REVEL	Benign	0.15
Sift	Benign	0.087	T;.;.;T;T;T;T;.
Sift4G	Uncertain	0.016	D;D;T;T;T;T;T;D
Polyphen		0.93	P;.;P;D;.;P;.;.
Vest4		0.80
MutPred		0.33		Gain of disorder (P = 0.062);Gain of disorder (P = 0.062);Gain of disorder (P = 0.062);.;.;Gain of disorder (P = 0.062);.;.;
MVP		0.50
MPC		0.82
ClinPred		0.79	D
GERP RS		4.7
Varity_R		0.25
gMVP		0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-58385098;