rs752321202

Variant names:

• chr3-58382688-G-A
• rs752321202
• NM_017771.5:c.376G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-58382688-G-A
• chr3-58382688-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017771.5(PXK):​c.376G>A​(p.Ala126Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000113 in 1,418,788 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: 31)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: PXK NM_017771.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.16

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23669621).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PXK	NM_017771.5	c.376G>A	p.Ala126Thr	missense_variant	Exon 4 of 18	ENST00000356151.7	NP_060241.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PXK	ENST00000356151.7	c.376G>A	p.Ala126Thr	missense_variant	Exon 4 of 18	1	NM_017771.5	ENSP00000348472.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.0000140 AC: 3 AN: 213926 Hom.: 0 AF XY: 0.00000857 AC XY: 1 AN XY: 116682

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000294

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000113 AC: 16 AN: 1418788 Hom.: 0 Cov.: 35 AF XY: 0.00000709 AC XY: 5 AN XY: 704944

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: 0.0000100

Gnomad4 OTH exome AF: 0.0000685

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0019	T;T;.;.;.;.;T
Eigen	Benign	-0.050
Eigen_PC	Benign	0.10
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	D;D;D;D;D;.;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.24	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;.;L;.;.;L;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.61	N;.;.;N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.38	T;.;.;T;T;T;T
Sift4G	Benign	0.55	T;T;T;T;T;T;T
Polyphen		0.43	B;.;P;P;.;P;.
Vest4		0.34
MutPred		0.34		Gain of glycosylation at Y128 (P = 0.0662);Gain of glycosylation at Y128 (P = 0.0662);Gain of glycosylation at Y128 (P = 0.0662);.;.;Gain of glycosylation at Y128 (P = 0.0662);.;
MVP		0.50
MPC		0.26
ClinPred		0.51	D
GERP RS		3.6
Varity_R		0.071
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs752321202; hg19: chr3-58368415;