rs201533636
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_000642.3(AGL):c.4076G>A(p.Arg1359His) variant causes a missense change. The variant allele was found at a frequency of 0.000235 in 1,613,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1359C) has been classified as Uncertain significance.
Frequency
Consequence
NM_000642.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGL | NM_000642.3 | c.4076G>A | p.Arg1359His | missense_variant | 30/34 | ENST00000361915.8 | |
LOC124904230 | XR_007066249.1 | n.1146-436C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGL | ENST00000361915.8 | c.4076G>A | p.Arg1359His | missense_variant | 30/34 | 1 | NM_000642.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000131 AC: 20AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000115 AC: 29AN: 251178Hom.: 0 AF XY: 0.000125 AC XY: 17AN XY: 135738
GnomAD4 exome AF: 0.000246 AC: 359AN: 1461794Hom.: 0 Cov.: 31 AF XY: 0.000265 AC XY: 193AN XY: 727208
GnomAD4 genome ? AF: 0.000131 AC: 20AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74328
ClinVar
Submissions by phenotype
Glycogen storage disease type III Uncertain:4
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 | Dec 28, 2021 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 24, 2022 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1359 of the AGL protein (p.Arg1359His). This variant is present in population databases (rs201533636, gnomAD 0.02%). 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: 526597). 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 expected to disrupt AGL protein function. 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 11, 2021 | The c.4076G>A (p.R1359H) alteration is located in exon 30 (coding exon 29) of the AGL gene. This alteration results from a G to A substitution at nucleotide position 4076, causing the arginine (R) at amino acid position 1359 to be replaced by a histidine (H). 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 | Nov 22, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge - |
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