Variant 15-77029688-C-T 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.562+114C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 1,218,290 control chromosomes in the GnomAD database, including 72,150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 7225 hom., cov: 32)

Exomes 𝑓: 0.34 ( 64925 hom. )

Consequence

PSTPIP1
NM_003978.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.11

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=-0.89).

BP6

Variant 15-77029688-C-T is Benign according to our data. Variant chr15-77029688-C-T is described in ClinVar as [Benign]. Clinvar id is 1254094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 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.562+114C>T		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.562+114C>T		intron_variant		1	NM_003978.5	ENSP00000452746.1		O43586-1

Frequencies

GnomAD3 genomes

AF:

0.292

AC:

44391

AN:

151936

Hom.:

7219

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.390

Gnomad AMR

AF:

0.295

Gnomad ASJ

AF:

0.364

Gnomad EAS

AF:

0.405

Gnomad SAS

AF:

0.278

Gnomad FIN

AF:

0.370

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.308

GnomAD4 exome

AF:

0.345

AC:

367481

AN:

1066236

Hom.:

64925

AF XY:

0.344

AC XY:

182034

AN XY:

529264

show subpopulations

Gnomad4 AFR exome

AF:

0.154

Gnomad4 AMR exome

AF:

0.312

Gnomad4 ASJ exome

AF:

0.372

Gnomad4 EAS exome

AF:

0.456

Gnomad4 SAS exome

AF:

0.285

Gnomad4 FIN exome

AF:

0.382

Gnomad4 NFE exome

AF:

0.349

Gnomad4 OTH exome

AF:

0.338

GnomAD4 genome

AF:

0.292

AC:

44421

AN:

152054

Hom.:

7225

Cov.:

AF XY:

0.294

AC XY:

21859

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.159

Gnomad4 AMR

AF:

0.295

Gnomad4 ASJ

AF:

0.364

Gnomad4 EAS

AF:

0.405

Gnomad4 SAS

AF:

0.278

Gnomad4 FIN

AF:

0.370

Gnomad4 NFE

AF:

0.347

Gnomad4 OTH

AF:

0.313

Alfa

AF:

0.321

Hom.:

1725

Bravo

AF:

0.285

Asia WGS

AF:

0.381

AC:

1324

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	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 28% of patients studied by a panel of primary immunodeficiencies. Number of patients: 27. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.68

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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