15-77032539-A-G

Position:

chr15-77032539-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003978.5(PSTPIP1):c.838+145A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 825,384 control chromosomes in the GnomAD database, including 167,542 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 27462 hom., cov: 33)

Exomes 𝑓: 0.64 ( 140080 hom. )

Consequence

PSTPIP1
NM_003978.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.894

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:

PSTPIP1 (HGNC:):

PSTPIP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 15-77032539-A-G is Benign according to our data. Variant chr15-77032539-A-G is described in ClinVar as [Benign]. Clinvar id is 440205.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSTPIP1	NM_003978.5 linkuse as main transcript	c.838+145A>G		intron_variant		ENST00000558012.6	NP_003969.2	O43586-1A0A0S2Z5P3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSTPIP1	ENST00000558012.6 linkuse as main transcript	c.838+145A>G		intron_variant		1	NM_003978.5	ENSP00000452746.1		O43586-1

Frequencies

GnomAD3 genomes

AF:

0.595

AC:

90411

AN:

151946

Hom.:

27437

Cov.:

show subpopulations

Gnomad AFR

AF:

0.493

Gnomad AMI

AF:

0.758

Gnomad AMR

AF:

0.541

Gnomad ASJ

AF:

0.696

Gnomad EAS

AF:

0.482

Gnomad SAS

AF:

0.559

Gnomad FIN

AF:

0.631

Gnomad MID

AF:

0.729

Gnomad NFE

AF:

0.666

Gnomad OTH

AF:

0.612

GnomAD3 exomes

AF:

0.603

AC:

49589

AN:

82188

Hom.:

15229

AF XY:

0.610

AC XY:

26202

AN XY:

42942

show subpopulations

Gnomad AFR exome

AF:

0.500

Gnomad AMR exome

AF:

0.533

Gnomad ASJ exome

AF:

0.696

Gnomad EAS exome

AF:

0.470

Gnomad SAS exome

AF:

0.592

Gnomad FIN exome

AF:

0.658

Gnomad NFE exome

AF:

0.671

Gnomad OTH exome

AF:

0.635

GnomAD4 exome

AF:

0.641

AC:

431466

AN:

673320

Hom.:

140080

Cov.:

AF XY:

0.640

AC XY:

220453

AN XY:

344558

show subpopulations

Gnomad4 AFR exome

AF:

0.488

Gnomad4 AMR exome

AF:

0.523

Gnomad4 ASJ exome

AF:

0.693

Gnomad4 EAS exome

AF:

0.528

Gnomad4 SAS exome

AF:

0.591

Gnomad4 FIN exome

AF:

0.652

Gnomad4 NFE exome

AF:

0.662

Gnomad4 OTH exome

AF:

0.638

GnomAD4 genome

AF:

0.595

AC:

90481

AN:

152064

Hom.:

27462

Cov.:

AF XY:

0.590

AC XY:

43840

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.494

Gnomad4 AMR

AF:

0.540

Gnomad4 ASJ

AF:

0.696

Gnomad4 EAS

AF:

0.482

Gnomad4 SAS

AF:

0.561

Gnomad4 FIN

AF:

0.631

Gnomad4 NFE

AF:

0.666

Gnomad4 OTH

AF:

0.612

Alfa

AF:

0.656

Hom.:

44064

Bravo

AF:

0.585

Asia WGS

AF:

0.574

AC:

1996

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 48% of patients studied by a panel of primary immunodeficiencies. Number of patients: 46. Only high quality variants are reported. -

Pyogenic arthritis-pyoderma gangrenosum-acne syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Jul 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.9

DANN

Benign

0.63

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

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