1-99870765-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_000642.3(AGL):c.854G>A(p.Arg285Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000473 in 1,597,672 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. R285R) has been classified as Likely benign.
Frequency
Consequence
NM_000642.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AGL | NM_000642.3 | c.854G>A | p.Arg285Gln | missense_variant | Exon 7 of 34 | ENST00000361915.8 | NP_000633.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000230 AC: 35AN: 151996Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000273 AC: 68AN: 249530Hom.: 0 AF XY: 0.000266 AC XY: 36AN XY: 135444
GnomAD4 exome AF: 0.000498 AC: 720AN: 1445676Hom.: 2 Cov.: 29 AF XY: 0.000460 AC XY: 331AN XY: 720252
GnomAD4 genome AF: 0.000230 AC: 35AN: 151996Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74226
ClinVar
Submissions by phenotype
Glycogen storage disease type III Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 17, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 285 of the AGL protein (p.Arg285Gln). This variant is present in population databases (rs144817648, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with AGL-related conditions. ClinVar contains an entry for this variant (Variation ID: 385974). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt AGL protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 16, 2019 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 11, 2021 | The c.854G>A (p.R285Q) alteration is located in exon 7 (coding exon 6) of the AGL gene. This alteration results from a G to A substitution at nucleotide position 854, causing the arginine (R) at amino acid position 285 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 14, 2018 | The R285Q variant in the AGL gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R285Q variant was not observed at any significant frequency in approximately 6,300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R285Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret R285Q as a variant of uncertain significance. - |
Meniere disease Uncertain:1
Uncertain significance, no assertion criteria provided | research | Center for Computational Biology & Bioinformatics, University of California, San Diego | Jun 03, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at