chr3-58391835-G-A

Variant names:

• chr3-58391835-G-A
• rs56401437
• NM_017771.5:c.603G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_017771.5(PXK):​c.603G>A​(p.Leu201Leu) 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
• Publications: 3 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 -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 Benign/Likely_benign. ClinVar VariationId is 718937.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 9 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.603G>A	p.Leu201Leu	synonymous	Exon 7 of 18	NP_060241.2
	PXK	NM_001349492.2		c.603G>A	p.Leu201Leu	synonymous	Exon 7 of 19	NP_001336421.1
	PXK	NM_001349493.2		c.603G>A	p.Leu201Leu	synonymous	Exon 7 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.603G>A	p.Leu201Leu	synonymous	Exon 7 of 18	ENSP00000348472.2	Q7Z7A4-1
	PXK	ENST00000302779.9	TSL:1	c.603G>A	p.Leu201Leu	synonymous	Exon 7 of 17	ENSP00000305045.6	W5RWE6
	PXK	ENST00000383716.7	TSL:1	c.603G>A	p.Leu201Leu	synonymous	Exon 7 of 19	ENSP00000373222.4	Q7Z7A4-2

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

GnomAD2 exomes AF: 0.00218 AC: 549 AN: 251304 AF XY: 0.00207

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 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

African (AFR) AF: 0.000329 AC: 11 AN: 33410

American (AMR) AF: 0.00152 AC: 68 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00796 AC: 208 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86188

European-Finnish (FIN) AF: 0.000899 AC: 48 AN: 53410

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5758

European-Non Finnish (NFE) AF: 0.00289 AC: 3205 AN: 1109544

Other (OTH) AF: 0.00164 AC: 99 AN: 60296

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

African (AFR) AF: 0.000674 AC: 28 AN: 41550

American (AMR) AF: 0.00196 AC: 30 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10600

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

European-Non Finnish (NFE) AF: 0.00278 AC: 189 AN: 68030

Other (OTH) AF: 0.000950 AC: 2 AN: 2106

Alfa AF: 0.00316 Hom.: 1

Bravo AF: 0.00199

EpiCase AF: 0.00224

EpiControl AF: 0.00379

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	6.8
DANN	Benign	0.69
PhyloP100		0.99
Mutation Taster		=99/1	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: rs56401437; hg19: chr3-58377562;