chr15-76994970-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The ENST00000559785.5(PSTPIP1):c.26+155C>T variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 1,200,650 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0074 ( 8 hom., cov: 32)
Exomes 𝑓: 0.00074 ( 8 hom. )
Consequence
PSTPIP1
ENST00000559785.5 intron, NMD_transcript
ENST00000559785.5 intron, NMD_transcript
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.76
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
Variant 15-76994970-C-T is Benign according to our data. Variant chr15-76994970-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1218031.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00744 (1132/152228) while in subpopulation AFR AF= 0.025 (1040/41524). AF 95% confidence interval is 0.0238. There are 8 homozygotes in gnomad4. There are 557 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1127 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PSTPIP1 | NM_001321137.1 | c.26+155C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PSTPIP1 | ENST00000559785.5 | c.26+155C>T | intron_variant, NMD_transcript_variant | 1 | |||||
PSTPIP1 | ENST00000558407.5 | c.26+155C>T | intron_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00741 AC: 1127AN: 152110Hom.: 8 Cov.: 32
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GnomAD4 exome AF: 0.000736 AC: 772AN: 1048422Hom.: 8 Cov.: 19 AF XY: 0.000670 AC XY: 343AN XY: 511994
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GnomAD4 genome ? AF: 0.00744 AC: 1132AN: 152228Hom.: 8 Cov.: 32 AF XY: 0.00748 AC XY: 557AN XY: 74444
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 24, 2018 | - - |
Computational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at