chr15-76995149-G-GCTGCCTGCCTGCCTGC

Variant names:

• chr15-76995149-G-GCTGCCTGCCTGCCTGC
• rs55909412
• NM_003978.5:c.-417_-402dupCCTGCCTGCCTGCCTG

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_003978.5(PSTPIP1):​c.-417_-402dupCCTGCCTGCCTGCCTG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000198 in 151,814 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00024 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PSTPIP1 NM_003978.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64
• Publications: 0 publications found

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]

PSTPIP1 Gene-Disease associations (from GenCC):

• pyogenic arthritis-pyoderma gangrenosum-acne syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• autoinflammatory syndrome

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• recurrent infections-inflammatory syndrome due to zinc metabolism disorder syndrome

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 30 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003978.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSTPIP1	NM_003978.5	MANE Select	c.-417_-402dupCCTGCCTGCCTGCCTG		5_prime_UTR	Exon 1 of 15	NP_003969.2
	PSTPIP1	NM_001411086.1		c.-417_-402dupCCTGCCTGCCTGCCTG		5_prime_UTR	Exon 1 of 15	NP_001398015.1	J3KPG6
	PSTPIP1	NM_001321136.2		c.-663_-648dupCCTGCCTGCCTGCCTG		5_prime_UTR	Exon 1 of 16	NP_001308065.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSTPIP1	ENST00000558012.6	TSL:1 MANE Select	c.-417_-402dupCCTGCCTGCCTGCCTG		5_prime_UTR	Exon 1 of 15	ENSP00000452746.1	O43586-1
	PSTPIP1	ENST00000559795.5	TSL:1	n.32_47dupCCTGCCTGCCTGCCTG		non_coding_transcript_exon	Exon 1 of 4
	PSTPIP1	ENST00000560223.5	TSL:1	n.-417_-402dupCCTGCCTGCCTGCCTG		non_coding_transcript_exon	Exon 1 of 16	ENSP00000454118.1	H0YNR2

Frequencies

GnomAD3 genomes AF: 0.000198 AC: 30 AN: 151702 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.0000950

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.000480

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000238 AC: 242 AN: 1018866 Hom.: 0 Cov.: 30 AF XY: 0.000255 AC XY: 124 AN XY: 486202

African (AFR) AF: 0.000142 AC: 3 AN: 21066

American (AMR) AF: 0.000103 AC: 1 AN: 9720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9444

East Asian (EAS) AF: 0.00 AC: 0 AN: 11952

South Asian (SAS) AF: 0.00119 AC: 64 AN: 53714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2288

European-Non Finnish (NFE) AF: 0.000192 AC: 166 AN: 865748

Other (OTH) AF: 0.000220 AC: 8 AN: 36368

GnomAD4 genome AF: 0.000198 AC: 30 AN: 151814 Hom.: 0 Cov.: 28 AF XY: 0.000202 AC XY: 15 AN XY: 74178

African (AFR) AF: 0.0000482 AC: 2 AN: 41470

American (AMR) AF: 0.000197 AC: 3 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5122

South Asian (SAS) AF: 0.00167 AC: 8 AN: 4800

European-Finnish (FIN) AF: 0.0000950 AC: 1 AN: 10524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 67858

Other (OTH) AF: 0.000475 AC: 1 AN: 2104

Alfa AF: 0.0000699 Hom.: 85

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6
Mutation Taster		=300/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs55909412; hg19: chr15-77287490;