chr15-76995454-G-A
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2
The NM_003978.5(PSTPIP1):c.-120G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000338 in 1,566,156 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000032 ( 1 hom. )
Consequence
PSTPIP1
NM_003978.5 5_prime_UTR
NM_003978.5 5_prime_UTR
Scores
2
1
7
Clinical Significance
Conservation
PhyloP100: -0.101
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 (MetaRNN=0.10967037).
BP6
Variant 15-76995454-G-A is Benign according to our data. Variant chr15-76995454-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1330610.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PSTPIP1 | NM_003978.5 | c.-120G>A | 5_prime_UTR_variant | 1/15 | ENST00000558012.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PSTPIP1 | ENST00000558012.6 | c.-120G>A | 5_prime_UTR_variant | 1/15 | 1 | NM_003978.5 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152230Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000422 AC: 8AN: 189618Hom.: 0 AF XY: 0.0000384 AC XY: 4AN XY: 104062
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GnomAD4 exome AF: 0.0000318 AC: 45AN: 1413808Hom.: 1 Cov.: 31 AF XY: 0.0000400 AC XY: 28AN XY: 699968
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GnomAD4 genome AF: 0.0000525 AC: 8AN: 152348Hom.: 0 Cov.: 33 AF XY: 0.0000805 AC XY: 6AN XY: 74492
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Pyogenic arthritis-pyoderma gangrenosum-acne syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 03, 2021 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MutationTaster
Benign
N;N;N
PROVEAN
Benign
N
Sift
Pathogenic
D
Sift4G
Pathogenic
D
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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