NM_017771.5:c.318T>C

Variant names:

• chr3-58382630-T-C
• rs56141849
• NM_017771.5:c.318T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_017771.5(PXK):​c.318T>C​(p.Asn106Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00487 in 1,601,098 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0050 (20 hom.)
• Consequence: PXK NM_017771.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.833
• Publications: 4 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 3-58382630-T-C is Benign according to our data. Variant chr3-58382630-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3770627.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 20 Unknown gene

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.318T>C	p.Asn106Asn	synonymous	Exon 4 of 18	NP_060241.2
	PXK	NM_001349492.2		c.318T>C	p.Asn106Asn	synonymous	Exon 4 of 19	NP_001336421.1
	PXK	NM_001349493.2		c.318T>C	p.Asn106Asn	synonymous	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.318T>C	p.Asn106Asn	synonymous	Exon 4 of 18	ENSP00000348472.2	Q7Z7A4-1
	PXK	ENST00000302779.9	TSL:1	c.318T>C	p.Asn106Asn	synonymous	Exon 4 of 17	ENSP00000305045.6	W5RWE6
	PXK	ENST00000383716.7	TSL:1	c.318T>C	p.Asn106Asn	synonymous	Exon 4 of 19	ENSP00000373222.4	Q7Z7A4-2

Frequencies

GnomAD3 genomes AF: 0.00365 AC: 554 AN: 151952 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00243

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.00861

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00523

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.00377 AC: 896 AN: 237542 AF XY: 0.00403

Gnomad AFR exome AF: 0.000963

Gnomad AMR exome AF: 0.00164

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000115

Gnomad FIN exome AF: 0.00742

Gnomad NFE exome AF: 0.00497

Gnomad OTH exome AF: 0.00616

GnomAD4 exome AF: 0.00500 AC: 7239 AN: 1449028 Hom.: 20 Cov.: 35 AF XY: 0.00492 AC XY: 3545 AN XY: 720602

African (AFR) AF: 0.000643 AC: 21 AN: 32660

American (AMR) AF: 0.00169 AC: 70 AN: 41366

Ashkenazi Jewish (ASJ) AF: 0.0000773 AC: 2 AN: 25858

East Asian (EAS) AF: 0.00 AC: 0 AN: 38980

South Asian (SAS) AF: 0.00330 AC: 274 AN: 83038

European-Finnish (FIN) AF: 0.00743 AC: 396 AN: 53302

Middle Eastern (MID) AF: 0.000523 AC: 3 AN: 5734

European-Non Finnish (NFE) AF: 0.00563 AC: 6238 AN: 1108202

Other (OTH) AF: 0.00392 AC: 235 AN: 59888

GnomAD4 genome AF: 0.00364 AC: 554 AN: 152070 Hom.: 1 Cov.: 31 AF XY: 0.00378 AC XY: 281 AN XY: 74324

African (AFR) AF: 0.00111 AC: 46 AN: 41492

American (AMR) AF: 0.00243 AC: 37 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00394 AC: 19 AN: 4826

European-Finnish (FIN) AF: 0.00861 AC: 91 AN: 10566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00524 AC: 356 AN: 67998

Other (OTH) AF: 0.00190 AC: 4 AN: 2108

Alfa AF: 0.00451 Hom.: 1

Bravo AF: 0.00305

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	7.5
DANN	Benign	0.60
PhyloP100		0.83
Mutation Taster		=96/4	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: rs56141849; hg19: chr3-58368357;