NM_003978.5(PSTPIP1):c.1146G>A (p.Ala382=) AND Pyogenic arthritis-pyoderma gangrenosum-acne syndrome

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Jun 16, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV001001205.3

Allele description [Variation Report for NM_003978.5(PSTPIP1):c.1146G>A (p.Ala382=)]

NM_003978.5(PSTPIP1):c.1146G>A (p.Ala382=)

Gene:
PSTPIP1:proline-serine-threonine phosphatase interacting protein 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q24.3
Genomic location:
Preferred name:
NM_003978.5(PSTPIP1):c.1146G>A (p.Ala382=)
HGVS:
  • NC_000015.10:g.77037071G>A
  • NG_007526.1:g.46948G>A
  • NM_001321135.2:c.1089G>A
  • NM_001321136.2:c.1119G>A
  • NM_001321137.1:c.1341G>A
  • NM_003978.5:c.1146G>AMANE SELECT
  • NP_001308064.1:p.Ala363=
  • NP_001308065.1:p.Ala373=
  • NP_001308066.1:p.Ala447=
  • NP_003969.2:p.Ala382=
  • LRG_172t1:c.1146G>A
  • LRG_172:g.46948G>A
  • NC_000015.9:g.77329412G>A
  • NM_003978.3:c.1146G>A
  • NR_135552.2:n.1326G>A
Links:
dbSNP: rs760234757
NCBI 1000 Genomes Browser:
rs760234757
Molecular consequence:
  • NR_135552.2:n.1326G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_001321135.2:c.1089G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001321136.2:c.1119G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001321137.1:c.1341G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_003978.5:c.1146G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:
Pyogenic arthritis-pyoderma gangrenosum-acne syndrome
Synonyms:
Pyogenic arthritis, pyoderma gangrenosum and acne; Pyogenic arthritis, pyoderma gangrenosum, and severe cystic acne; Familial recurrent arthritis
Identifiers:
MONDO: MONDO:0011462; MedGen: C1858361; Orphanet: 69126; OMIM: 604416

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001091241Invitaecriteria provided, single submitter
Likely benign
(Jun 16, 2020)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001158365ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratoriescriteria provided, single submitter
Uncertain significance
(Apr 19, 2019)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001091241.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories, SCV001158365.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The PSTPIP1 c.1146G>A; p.Ala382Ala variant (rs760234757), to our knowledge, is not reported in the medical literature or gene-specific databases. The variant is reported in the general population with an overall allele frequency of 0.007% (20/278196 alleles) in the Genome Aggregation Database. This is a synonymous variant in a weakly conserved nucleotide, but computational analyses (Alamut v.2.11) predict that this variant may create a novel splicing acceptor site, which if utilized would create a frameshift. However, pathogenic variants in PSTPIP1 are most often missense variants, not loss of function variants as this variant would induce if the novel splicing acceptor site were utilized (Campbell 2016). Therefore, due to limited information, the clinical significance of this variant cannot be determined with certainty. REFERENCES: Campbell L et al. The Relationship between NALP3 and Autoinflammatory Syndromes. Int J Mol Sci. 2016 May 13;17(5). pii: E725.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 7, 2021

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