3-58391835-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_017771.5(PXK):c.603G>A(p.Leu201=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00243 in 1,611,352 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (9 hom.)
• Consequence: PXK NM_017771.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.988

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 3-58391835-G-A is Benign according to our data. Variant chr3-58391835-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 718937.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PXK	NM_017771.5	c.603G>A	p.Leu201=	synonymous_variant	7/18	ENST00000356151.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PXK	ENST00000356151.7	c.603G>A	p.Leu201=	synonymous_variant	7/18	1	NM_017771.5	P1

Frequencies

GnomAD3 genomes AF: 0.00179 AC: 273 AN: 152136 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000676

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00278

Gnomad OTH AF: 0.000960

GnomAD3 exomes AF: 0.00218 AC: 549 AN: 251304 Hom.: 3 AF XY: 0.00207 AC XY: 281 AN XY: 135826

Gnomad AFR exome AF: 0.000739

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.00824

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.000647

Gnomad NFE exome AF: 0.00328

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00250 AC: 3643 AN: 1459098 Hom.: 9 Cov.: 30 AF XY: 0.00242 AC XY: 1756 AN XY: 726006

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.00152

Gnomad4 ASJ exome AF: 0.00796

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.000899

Gnomad4 NFE exome AF: 0.00289

Gnomad4 OTH exome AF: 0.00164

GnomAD4 genome AF: 0.00179 AC: 273 AN: 152254 Hom.: 0 Cov.: 33 AF XY: 0.00164 AC XY: 122 AN XY: 74434

Gnomad4 AFR AF: 0.000674

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00278

Gnomad4 OTH AF: 0.000950

Alfa AF: 0.00316 Hom.: 1

Bravo AF: 0.00199

EpiCase AF: 0.00224

EpiControl AF: 0.00379

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 20, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	PXK: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	6.8
Dann	Benign	0.69

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

LitVar

Other links and lift over

dbSNP: rs56401437; hg19: chr3-58377562;