rs201186216
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_003978.5(PSTPIP1):c.1054G>A(p.Glu352Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000223 in 1,610,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E352A) has been classified as Uncertain significance.
Frequency
Consequence
NM_003978.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PSTPIP1 | NM_003978.5 | c.1054G>A | p.Glu352Lys | missense_variant | 14/15 | ENST00000558012.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PSTPIP1 | ENST00000558012.6 | c.1054G>A | p.Glu352Lys | missense_variant | 14/15 | 1 | NM_003978.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000132 AC: 20AN: 152008Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000330 AC: 81AN: 245714Hom.: 0 AF XY: 0.000358 AC XY: 48AN XY: 134000
GnomAD4 exome AF: 0.000233 AC: 340AN: 1458564Hom.: 0 Cov.: 34 AF XY: 0.000263 AC XY: 191AN XY: 725516
GnomAD4 genome ? AF: 0.000125 AC: 19AN: 152126Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7AN XY: 74380
ClinVar
Submissions by phenotype
Pyogenic arthritis-pyoderma gangrenosum-acne syndrome Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Apr 08, 2022 | The PSTPIP1 c.1054G>A; p.Glu352Lys variant (rs201186216) is reported in the literature in an individual affected with systemic auto-inflammatory disease (Rusmini 2016) but the variant was not determined to be causative. This variant is also reported in ClinVar (Variation ID: 317183) and is found in the general population with an allele frequency of 0.03% (83/277034 alleles) in the Genome Aggregation database. The glutamic acid at codon 352 is weakly conserved, and computational analyses predict that this variant is neutral (REVEL: 0.078). Due to limited information, the clinical significance of the p.Glu352Lys variant is uncertain at this time. Reference: Rusmini M et al. Next-generation sequencing and its initial applications for molecular diagnosis of systemic auto-inflammatory diseases. Ann Rheum Dis. 2016 Aug;75(8):1550-7. PMID: 26386126. - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 02, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | PSTPIP1: BP4 - |
Autoinflammatory syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | May 25, 2021 | - - |
PSTPIP1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 01, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at