15-76994970-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001321137.1(PSTPIP1):​c.26+155C>T variant causes a intron 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
NM_001321137.1 intron

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.76
Variant links:
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 -20 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_multiple_submitters_no_conflicts, 2 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 GnomAd4 at 1132 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PSTPIP1NM_003978.5 linkc.-604C>T upstream_gene_variant ENST00000558012.6 NP_003969.2 O43586-1A0A0S2Z5P3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PSTPIP1ENST00000558012.6 linkc.-604C>T upstream_gene_variant 1 NM_003978.5 ENSP00000452746.1 O43586-1

Frequencies

GnomAD3 genomes
AF:
0.00741
AC:
1127
AN:
152110
Hom.:
8
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0250
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00432
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.00669
GnomAD4 exome
AF:
0.000736
AC:
772
AN:
1048422
Hom.:
8
Cov.:
19
AF XY:
0.000670
AC XY:
343
AN XY:
511994
show subpopulations
Gnomad4 AFR exome
AF:
0.0255
Gnomad4 AMR exome
AF:
0.00260
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000593
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000974
Gnomad4 OTH exome
AF:
0.00153
GnomAD4 genome
AF:
0.00744
AC:
1132
AN:
152228
Hom.:
8
Cov.:
32
AF XY:
0.00748
AC XY:
557
AN XY:
74444
show subpopulations
Gnomad4 AFR
AF:
0.0250
Gnomad4 AMR
AF:
0.00431
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.00662
Alfa
AF:
0.00455
Hom.:
0
Bravo
AF:
0.00859
Asia WGS
AF:
0.00144
AC:
5
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Oct 24, 2018
GeneDx
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.12
DANN
Benign
0.35

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs115845814; hg19: chr15-77287311; API