ClinVar Miner

Submissions for variant NM_003978.5(PSTPIP1):c.146C>T (p.Ala49Val)

gnomAD frequency: 0.00001  dbSNP: rs756426938
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521154 SCV000620445 uncertain significance not provided 2021-03-23 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function
Invitae RCV001209843 SCV001381295 uncertain significance Pyogenic arthritis-pyoderma gangrenosum-acne syndrome 2023-12-13 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 49 of the PSTPIP1 protein (p.Ala49Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with PSTPIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 451711). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PSTPIP1 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001209843 SCV001472154 uncertain significance Pyogenic arthritis-pyoderma gangrenosum-acne syndrome 2019-09-15 criteria provided, single submitter clinical testing The PSTPIP1 c.146C>T; p.Ala49Val variant (rs756426938), to our knowledge, is not reported in the medical literature but is reported in an individual with an autoinflammatory disease in a gene-specific database (see link below). The variant is reported in the ClinVar database (Variation ID: 451711) and in the general population with an overall allele frequency of 0.0017% (4/230,060 alleles) in the Genome Aggregation Database. The alanine at this position is moderately conserved and computational analyses (SIFT: Tolerated, PolyPhen-2: Possibly Damaging) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of this variant cannot be determined. References: Link to Infevers database: https://infevers.umai-montpellier.fr/web/search.php?n=5

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