rs748314171

Variant names:

• chr3-58399352-A-C
• rs748314171
• NM_017771.5:c.1156A>C

Your query was ambiguous. Multiple possible variants found:

• chr3-58399352-A-C
• chr3-58399352-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.1156A>C​(p.Thr386Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: PXK NM_017771.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46

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=0.33264533).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PXK	NM_017771.5	c.1156A>C	p.Thr386Pro	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.1156A>C	p.Thr386Pro	missense_variant	Exon 12 of 18	1	NM_017771.5	ENSP00000348472.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.081	T;T;.;.;.;.;T;T
Eigen	Benign	0.072
Eigen_PC	Benign	0.092
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D;D;D;D;D;.;D;D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.33	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.4	M;.;M;.;.;M;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.7	D;N;.;D;D;D;D;.
REVEL	Benign	0.21
Sift	Uncertain	0.0020	D;T;.;D;D;D;D;.
Sift4G	Uncertain	0.0040	D;D;D;D;D;D;D;D
Polyphen		0.99	D;.;D;B;.;D;.;.
Vest4		0.59
MutPred		0.57		Gain of catalytic residue at P385 (P = 0.0107);Gain of catalytic residue at P385 (P = 0.0107);Gain of catalytic residue at P385 (P = 0.0107);.;.;Gain of catalytic residue at P385 (P = 0.0107);.;.;
MVP		0.51
MPC		1.0
ClinPred		0.98	D
GERP RS		3.5
Varity_R		0.51
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs748314171; hg19: chr3-58385079;