rs747139033
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_003978.5(PSTPIP1):c.1120-9C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000403 in 1,611,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000039 ( 0 hom. )
Consequence
PSTPIP1
NM_003978.5 splice_polypyrimidine_tract, intron
NM_003978.5 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.001985
2
Clinical Significance
Conservation
PhyloP100: 0.573
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 -8 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BS2
?
High AC in GnomAd at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PSTPIP1 | NM_003978.5 | c.1120-9C>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000558012.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PSTPIP1 | ENST00000558012.6 | c.1120-9C>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_003978.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152188Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000244 AC: 6AN: 245704Hom.: 0 AF XY: 0.00000746 AC XY: 1AN XY: 134004
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GnomAD4 exome AF: 0.0000391 AC: 57AN: 1459428Hom.: 0 Cov.: 31 AF XY: 0.0000386 AC XY: 28AN XY: 725952
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GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74352
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Pyogenic arthritis-pyoderma gangrenosum-acne syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 04, 2023 | This variant has not been reported in the literature in individuals affected with PSTPIP1-related conditions. This variant is present in population databases (rs747139033, gnomAD 0.005%). This sequence change falls in intron 14 of the PSTPIP1 gene. It does not directly change the encoded amino acid sequence of the PSTPIP1 protein. ClinVar contains an entry for this variant (Variation ID: 466413). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. - |
Computational scores
Source:
Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Calibrated prediction
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -29
Find out detailed SpliceAI scores and Pangolin per-transcript scores at