rs137943515
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM5PP3
The NM_000642.3(AGL):c.1028G>A(p.Arg343Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000424 in 1,603,240 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic 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. R343W) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000642.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AGL | NM_000642.3 | c.1028G>A | p.Arg343Gln | missense_variant | Exon 8 of 34 | ENST00000361915.8 | NP_000633.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000443 AC: 66AN: 148964Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.000422 AC: 106AN: 251306Hom.: 0 AF XY: 0.000442 AC XY: 60AN XY: 135836
GnomAD4 exome AF: 0.000422 AC: 613AN: 1454156Hom.: 0 Cov.: 33 AF XY: 0.000444 AC XY: 321AN XY: 723428
GnomAD4 genome AF: 0.000449 AC: 67AN: 149084Hom.: 1 Cov.: 33 AF XY: 0.000384 AC XY: 28AN XY: 72846
ClinVar
Submissions by phenotype
not provided Uncertain:5
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Sep 25, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Oct 21, 2022 | PM2 - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 01, 2020 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function - |
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Mar 30, 2022 | The AGL c.1028G>A; p.Arg343Gln variant (rs137943515), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 445557). This variant is found in the general population with an overall allele frequency of 0.05% (129/282664 alleles) in the Genome Aggregation Database. The arginine at codon 343 is highly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.659). Due to limited information, the clinical significance of this variant is uncertain at this time. - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2023 | AGL: PM5 - |
Glycogen storage disease type III Uncertain:4Benign:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jan 07, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 28, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 22, 2025 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 04, 2022 | The c.1028G>A (p.R343Q) alteration is located in exon 8 (coding exon 7) of the AGL gene. This alteration results from a G to A substitution at nucleotide position 1028, causing the arginine (R) at amino acid position 343 to be replaced by a glutamine (Q). 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