ClinVar Miner

Submissions for variant NM_015599.3(PGM3):c.1354C>A (p.Leu452Ile)

gnomAD frequency: 0.00061  dbSNP: rs201593125
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics RCV000514778 SCV000609888 uncertain significance not provided 2017-03-17 criteria provided, single submitter clinical testing
Invitae RCV000693318 SCV000821182 uncertain significance Immunodeficiency 23 2022-10-22 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 480 of the PGM3 protein (p.Leu480Ile). This variant is present in population databases (rs201593125, gnomAD 0.09%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with PGM3-related conditions. ClinVar contains an entry for this variant (Variation ID: 445475). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
Baylor Genetics RCV000693318 SCV001527848 uncertain significance Immunodeficiency 23 2018-08-27 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Fulgent Genetics, Fulgent Genetics RCV000693318 SCV002799674 uncertain significance Immunodeficiency 23 2022-03-30 criteria provided, single submitter clinical testing
Ambry Genetics RCV002524978 SCV003676392 uncertain significance Inborn genetic diseases 2020-11-18 criteria provided, single submitter clinical testing The c.1438C>A (p.L480I) alteration is located in exon 12 (coding exon 11) of the PGM3 gene. This alteration results from a C to A substitution at nucleotide position 1438, causing the leucine (L) at amino acid position 480 to be replaced by an isoleucine (I). Based on data from the Genome Aggregation Database (gnomAD) database, the PGM3 c.1438C>A alteration was observed in 0.06% (171/282058) of total alleles studied, with a frequency of 0.08% (30/35304) in the Latino subpopulation. This amino acid position is highly conserved in available vertebrate species. The p.L480I alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GenomeConnect - Invitae Patient Insights Network RCV000693318 SCV001749484 not provided Immunodeficiency 23 no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 08-15-2018 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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