rs200771233

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_003978.5(PSTPIP1):c.1151A>G(p.Asp384Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000666 in 1,612,240 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D384N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00049 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00068 ( 5 hom. )

Consequence

PSTPIP1
NM_003978.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 8.37

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

pyogenic arthritis-pyoderma gangrenosum-acne syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
autoinflammatory syndrome
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
recurrent infections-inflammatory syndrome due to zinc metabolism disorder syndrome
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

PSTPIP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.067043245).

BP6

Variant 15-77037076-A-G is Benign according to our data. Variant chr15-77037076-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 242305.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 75 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003978.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PSTPIP1	NM_003978.5	MANE Select	c.1151A>G	p.Asp384Gly	missense	Exon 15 of 15	NP_003969.2
PSTPIP1	NM_001321137.1		c.1346A>G	p.Asp449Gly	missense	Exon 16 of 16	NP_001308066.1	O43586
PSTPIP1	NM_001411086.1		c.1142A>G	p.Asp381Gly	missense	Exon 15 of 15	NP_001398015.1	J3KPG6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PSTPIP1	ENST00000558012.6	TSL:1 MANE Select	c.1151A>G	p.Asp384Gly	missense	Exon 15 of 15	ENSP00000452746.1	O43586-1
PSTPIP1	ENST00000559295.5	TSL:1	c.1094A>G	p.Asp365Gly	missense	Exon 14 of 14	ENSP00000452743.1	O43586-2
PSTPIP1	ENST00000558870.1	TSL:1	c.299A>G	p.Asp100Gly	missense	Exon 4 of 4	ENSP00000452779.1	H0YKF1

Frequencies

GnomAD3 genomes

AF:

0.000493

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00786

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.00114

AC:

282

AN:

246980

AF XY:

0.00152

show subpopulations

Gnomad AFR exome

AF:

0.0000652

Gnomad AMR exome

AF:

0.000638

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000306

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.000684

AC:

998

AN:

1460026

Hom.:

Cov.:

AF XY:

0.000917

AC XY:

666

AN XY:

726276

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.000738

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00738

AC:

637

AN:

86256

European-Finnish (FIN)

AF:

0.0000384

AC:

AN:

52040

Middle Eastern (MID)

AF:

0.00486

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000220

AC:

245

AN:

1111634

Other (OTH)

AF:

0.000845

AC:

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

105

157

210

262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000493

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.000645

AC XY:

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

41524

American (AMR)

AF:

0.000719

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00786

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000250

AC:

AN:

68000

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000381

Hom.:

Bravo

AF:

0.000329

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000478

AC:

ExAC

AF:

0.00118

AC:

142

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000474

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (6)

Pyogenic arthritis-pyoderma gangrenosum-acne syndrome (2)

Autoinflammatory syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Uncertain

0.032

BayesDel_noAF

Pathogenic

0.28

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.89

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.067

MetaSVM

Uncertain

0.17

MutationAssessor

Pathogenic

3.2

PhyloP100

8.4

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-3.1

REVEL

Uncertain

0.51

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0070

Polyphen

0.95

Vest4

0.84

MVP

0.88

MPC

0.72

ClinPred

0.12

GERP RS

4.5

Varity_R

0.37

gMVP

0.82

Mutation Taster

=84/16

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over