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

gnomAD frequency: 0.00061  dbSNP: rs201593125

Total submissions: 8

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
Labcorp Genetics (formerly Invitae), Labcorp	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.
Breakthrough Genomics, Breakthrough Genomics	RCV000514778	SCV005189146	uncertain significance	not provided		criteria provided, single submitter	not provided
CeGaT Center for Human Genetics Tuebingen	RCV000514778	SCV005435785	uncertain significance	not provided	2024-11-01	criteria provided, single submitter	clinical testing
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.