rs529402949
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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.Leu378=) 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
NM_003978.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.42
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]
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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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PSTPIP1 | NM_003978.5 | c.1134G>A | p.Leu378= | synonymous_variant | 15/15 | ENST00000558012.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PSTPIP1 | ENST00000558012.6 | c.1134G>A | p.Leu378= | synonymous_variant | 15/15 | 1 | NM_003978.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000835 AC: 127AN: 152186Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00110 AC: 271AN: 246542Hom.: 1 AF XY: 0.00103 AC XY: 138AN XY: 134456
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GnomAD4 exome AF: 0.000518 AC: 756AN: 1459918Hom.: 3 Cov.: 31 AF XY: 0.000515 AC XY: 374AN XY: 726228
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GnomAD4 genome ? AF: 0.000834 AC: 127AN: 152302Hom.: 0 Cov.: 32 AF XY: 0.00114 AC XY: 85AN XY: 74476
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Dec 01, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | PSTPIP1: BP4 - |
Pyogenic arthritis-pyoderma gangrenosum-acne syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 20, 2024 | - - |
Autoinflammatory syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Apr 12, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at