15-76995149-G-GCTGCCTGCCTGC

Position:

• chr15-76995149-G-GCTGCCTGCCTGC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_003978.5(PSTPIP1):​c.-413_-402dupCCTGCCTGCCTG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 151,758 control chromosomes in the GnomAD database, including 1,379 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1379 hom., cov: 28)
  • Exomes 𝑓: 0.15 (10633 hom.)
  • Failed GnomAD Quality Control
• Consequence: PSTPIP1 NM_003978.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.64

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 15-76995149-G-GCTGCCTGCCTGC is Benign according to our data. Variant chr15-76995149-G-GCTGCCTGCCTGC is described in ClinVar as [Benign]. Clinvar id is 317164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSTPIP1	NM_003978.5	c.-413_-402dupCCTGCCTGCCTG		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.-413_-402dupCCTGCCTGCCTG		5_prime_UTR_variant	1/15	1	NM_003978.5	ENSP00000452746.1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18556 AN: 151646 Hom.: 1372 Cov.: 28

Gnomad AFR AF: 0.0486

Gnomad AMI AF: 0.0615

Gnomad AMR AF: 0.0944

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.0878

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.128

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.152 AC: 154785 AN: 1018526 Hom.: 10633 Cov.: 30 AF XY: 0.154 AC XY: 74657 AN XY: 486004

Gnomad4 AFR exome AF: 0.0413

Gnomad4 AMR exome AF: 0.0866

Gnomad4 ASJ exome AF: 0.171

Gnomad4 EAS exome AF: 0.0849

Gnomad4 SAS exome AF: 0.212

Gnomad4 FIN exome AF: 0.164

Gnomad4 NFE exome AF: 0.152

Gnomad4 OTH exome AF: 0.151

GnomAD4 genome AF: 0.122 AC: 18566 AN: 151758 Hom.: 1379 Cov.: 28 AF XY: 0.124 AC XY: 9163 AN XY: 74140

Gnomad4 AFR AF: 0.0485

Gnomad4 AMR AF: 0.0940

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.0875

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.133

Bravo AF: 0.109

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 21, 2019

- -

Pyogenic arthritis-pyoderma gangrenosum-acne syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs55909412; hg19: chr15-77287490;