chr6-83171948-G-T
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_015599.3(PGM3):c.1354C>A(p.Leu452Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000761 in 1,612,912 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_015599.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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PGM3 | ENST00000513973.6 | c.1354C>A | p.Leu452Ile | missense_variant | Exon 11 of 13 | 1 | NM_015599.3 | ENSP00000424874.1 | ||
PGM3 | ENST00000283977.9 | c.1111C>A | p.Leu371Ile | missense_variant | Exon 10 of 12 | 5 | ENSP00000283977.5 |
Frequencies
GnomAD3 genomes AF: 0.000624 AC: 95AN: 152178Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000618 AC: 155AN: 250656Hom.: 0 AF XY: 0.000613 AC XY: 83AN XY: 135406
GnomAD4 exome AF: 0.000775 AC: 1132AN: 1460616Hom.: 4 Cov.: 29 AF XY: 0.000758 AC XY: 551AN XY: 726610
GnomAD4 genome AF: 0.000624 AC: 95AN: 152296Hom.: 0 Cov.: 33 AF XY: 0.000644 AC XY: 48AN XY: 74480
ClinVar
Submissions by phenotype
Immunodeficiency 23 Uncertain:3Other:1
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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This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -
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. -
not provided Uncertain:3
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Inborn genetic diseases Uncertain:1
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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at