Variant 15-76995677-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_003978.5(PSTPIP1):c.36+68G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,609,522 control chromosomes in the GnomAD database, including 50,599 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7798 hom., cov: 33)

Exomes 𝑓: 0.23 ( 42801 hom. )

Consequence

PSTPIP1
NM_003978.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.77

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=-0.81).

BP6

Variant 15-76995677-G-A is Benign according to our data. Variant chr15-76995677-G-A is described in ClinVar as [Benign]. Clinvar id is 1182295.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.503 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.36+68G>A		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.36+68G>A		intron_variant		1	NM_003978.5	ENSP00000452746.1		O43586-1

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

45100

AN:

152072

Hom.:

7777

Cov.:

show subpopulations

Gnomad AFR

AF:

0.436

Gnomad AMI

AF:

0.117

Gnomad AMR

AF:

0.371

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.519

Gnomad SAS

AF:

0.325

Gnomad FIN

AF:

0.221

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.199

Gnomad OTH

AF:

0.269

GnomAD4 exome

AF:

0.229

AC:

333063

AN:

1457332

Hom.:

42801

AF XY:

0.227

AC XY:

164704

AN XY:

725124

show subpopulations

Gnomad4 AFR exome

AF:

0.442

Gnomad4 AMR exome

AF:

0.452

Gnomad4 ASJ exome

AF:

0.159

Gnomad4 EAS exome

AF:

0.488

Gnomad4 SAS exome

AF:

0.290

Gnomad4 FIN exome

AF:

0.214

Gnomad4 NFE exome

AF:

0.201

Gnomad4 OTH exome

AF:

0.238

GnomAD4 genome

AF:

0.297

AC:

45149

AN:

152190

Hom.:

7798

Cov.:

AF XY:

0.302

AC XY:

22474

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.435

Gnomad4 AMR

AF:

0.372

Gnomad4 ASJ

AF:

0.168

Gnomad4 EAS

AF:

0.519

Gnomad4 SAS

AF:

0.323

Gnomad4 FIN

AF:

0.221

Gnomad4 NFE

AF:

0.199

Gnomad4 OTH

AF:

0.267

Alfa

AF:

0.252

Hom.:

894

Bravo

AF:

0.313

Asia WGS

AF:

0.411

AC:

1426

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	Mar 03, 2015	- -

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 61% of patients studied by a panel of primary immunodeficiencies. Number of patients: 59. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.22

DANN

Benign

0.42

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