15-76995403-A-T
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_003978.5(PSTPIP1):c.-171A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000134 in 1,463,650 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00014 ( 2 hom. )
Consequence
PSTPIP1
NM_003978.5 5_prime_UTR_premature_start_codon_gain
NM_003978.5 5_prime_UTR_premature_start_codon_gain
Scores
5
Splicing: ADA: 0.00003376
2
Clinical Significance
Conservation
PhyloP100: -0.554
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 -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_addAF=-0.71721).
BP6
Variant 15-76995403-A-T is Benign according to our data. Variant chr15-76995403-A-T is described in ClinVar as [Benign]. Clinvar id is 317167.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 11 AD gene.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| PSTPIP1 | NM_003978.5 | c.-171A>T | 5_prime_UTR_premature_start_codon_gain_variant | 1/15 | ENST00000558012.6 | NP_003969.2 | ||
| PSTPIP1 | NM_003978.5 | c.-171A>T | 5_prime_UTR_variant | 1/15 | ENST00000558012.6 | NP_003969.2 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| PSTPIP1 | ENST00000558012 | c.-171A>T | 5_prime_UTR_premature_start_codon_gain_variant | 1/15 | 1 | NM_003978.5 | ENSP00000452746.1 | |||
| PSTPIP1 | ENST00000558012 | c.-171A>T | 5_prime_UTR_variant | 1/15 | 1 | NM_003978.5 | ENSP00000452746.1 |
Frequencies
GnomAD3 genomes 0.0000723 AC: 11AN: 152190Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000379 AC: 33AN: 86978Hom.: 1 AF XY: 0.000379 AC XY: 17AN XY: 44876
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GnomAD4 exome AF: 0.000141 AC: 185AN: 1311342Hom.: 2 Cov.: 31 AF XY: 0.000206 AC XY: 132AN XY: 639752
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GnomAD4 genome 0.0000722 AC: 11AN: 152308Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8AN XY: 74466
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Pyogenic arthritis-pyoderma gangrenosum-acne syndrome Benign:1
| Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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Name
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BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
FATHMM_MKL
Benign
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at