rs529402949

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_003978.5(PSTPIP1):c.1134G>A(p.Leu378Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.000548 in 1,612,220 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00083 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00052 ( 3 hom. )

Consequence

PSTPIP1
NM_003978.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 4.42

Variant links:

Genes affected

PSTPIP1 (HGNC:9580): (proline-serine-threonine phosphatase interacting protein 1) This gene encodes a cytoskeletal protein that is highly expressed in hemopoietic tissues. This protein functions via its interaction with several different proteins involved in cytoskeletal organization and inflammatory processes. It binds to the cytoplasmic tail of CD2, an effector of T cell activation and adhesion, downregulating CD2-triggered adhesion. It binds PEST-type protein tyrosine phosphatases (PTP) and directs them to c-Abl kinase to mediate c-Abl dephosphorylation, thereby, regulating c-Abl activity. It also interacts with pyrin, which is found in association with the cytoskeleton in myeloid/monocytic cells and modulates immunoregulatory functions. Mutations in this gene are associated with PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. It is hypothesized that the disease-causing mutations compromise physiologic signaling necessary for the maintenance of a proper inflammatory response. [provided by RefSeq, Mar 2016]

PSTPIP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 15-77037059-G-A is Benign according to our data. Variant chr15-77037059-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 534753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-77037059-G-A is described in Lovd as [Benign].

BS2

High AC in GnomAd4 at 127 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSTPIP1	NM_003978.5 link	c.1134G>A	p.Leu378Leu	synonymous_variant	Exon 15 of 15	ENST00000558012.6	NP_003969.2	O43586-1A0A0S2Z5P3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSTPIP1	ENST00000558012.6 link	c.1134G>A	p.Leu378Leu	synonymous_variant	Exon 15 of 15	1	NM_003978.5	ENSP00000452746.1		O43586-1

Frequencies

GnomAD3 genomes

AF:

0.000835

AC:

127

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00250

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00110

AC:

271

AN:

246542

Hom.:

AF XY:

0.00103

AC XY:

138

AN XY:

134456

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00111

Gnomad EAS exome

AF:

0.000445

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.00899

Gnomad NFE exome

AF:

0.000361

Gnomad OTH exome

AF:

0.00100

GnomAD4 exome

AF:

0.000518

AC:

756

AN:

1459918

Hom.:

Cov.:

AF XY:

0.000515

AC XY:

374

AN XY:

726228

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00138

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.000325

Gnomad4 FIN exome

AF:

0.00873

Gnomad4 NFE exome

AF:

0.000156

Gnomad4 OTH exome

AF:

0.000796

GnomAD4 genome

AF:

0.000834

AC:

127

AN:

152302

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00251

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00753

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000504

Hom.:

Bravo

AF:

0.000125

Asia WGS

AF:

0.00635

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PSTPIP1: BP4 -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Pyogenic arthritis-pyoderma gangrenosum-acne syndrome

Benign:2

Dec 12, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 04, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autoinflammatory syndrome

Benign:1

Apr 12, 2021

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.5

DANN

Benign

0.63

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over