ClinVar Miner

Submissions for variant NM_003978.5(PSTPIP1):c.586G>A (p.Ala196Thr)

gnomAD frequency: 0.00002  dbSNP: rs758911910
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000350743 SCV000393999 benign Pyogenic arthritis-pyoderma gangrenosum-acne syndrome 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae RCV000350743 SCV001229115 uncertain significance Pyogenic arthritis-pyoderma gangrenosum-acne syndrome 2021-09-18 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 317177). This variant has not been reported in the literature in individuals affected with PSTPIP1-related conditions. This variant is present in population databases (rs758911910, ExAC 0.04%). This sequence change replaces alanine with threonine at codon 196 of the PSTPIP1 protein (p.Ala196Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000350743 SCV001473607 uncertain significance Pyogenic arthritis-pyoderma gangrenosum-acne syndrome 2020-04-30 criteria provided, single submitter clinical testing The PSTPIP1 c.586G>A; p.Ala196Thr variant (rs758911910), to our knowledge, is not reported in the medical literature or gene specific databases. The variant is reported in the ClinVar database (Variation ID: 317177) and in the general population with an overall allele frequency of 0.002429% (6/247,002 alleles) in the Genome Aggregation Database. The alanine at codon 196 is weakly conserved and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Due to limited information, the clinical significance of the p.Ala196Thr variant is uncertain at this time.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002263000 SCV002542886 uncertain significance Autoinflammatory syndrome 2017-11-01 criteria provided, single submitter clinical testing

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