rs8030698

Variant names:

• chr15-77011398-T-C
• rs8030698
• NM_003978.5:c.37-6750T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-77011398-T-C
• chr15-77011398-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003978.5(PSTPIP1):​c.37-6750T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 152,134 control chromosomes in the GnomAD database, including 36,155 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.66 (36155 hom., cov: 33)
• Consequence: PSTPIP1 NM_003978.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.436
• Publications: 2 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: G2P, Orphanet, 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

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.37-6750T>C		intron	N/A	NP_003969.2
	PSTPIP1	NM_001321137.1		c.232-6750T>C		intron	N/A	NP_001308066.1
	PSTPIP1	NM_001411086.1		c.37-6750T>C		intron	N/A	NP_001398015.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSTPIP1	ENST00000558012.6	TSL:1 MANE Select	c.37-6750T>C		intron	N/A	ENSP00000452746.1
	PSTPIP1	ENST00000559295.5	TSL:1	c.37-6750T>C		intron	N/A	ENSP00000452743.1
	PSTPIP1	ENST00000559785.5	TSL:1	n.232-6750T>C		intron	N/A	ENSP00000452986.1

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100888 AN: 152016 Hom.: 36148 Cov.: 33

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.887

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.836

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.701

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.663 AC: 100927 AN: 152134 Hom.: 36155 Cov.: 33 AF XY: 0.660 AC XY: 49121 AN XY: 74372

African (AFR) AF: 0.397 AC: 16468 AN: 41494

American (AMR) AF: 0.613 AC: 9373 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.836 AC: 2901 AN: 3472

East Asian (EAS) AF: 0.501 AC: 2580 AN: 5152

South Asian (SAS) AF: 0.682 AC: 3288 AN: 4822

European-Finnish (FIN) AF: 0.796 AC: 8431 AN: 10596

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.814 AC: 55340 AN: 67988

Other (OTH) AF: 0.703 AC: 1487 AN: 2114

Alfa AF: 0.732 Hom.: 5284

Bravo AF: 0.639

Asia WGS AF: 0.592 AC: 2060 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.24
DANN	Benign	0.27
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs8030698; hg19: chr15-77303739;