rs538916479
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000642.3(AGL):c.1424G>A(p.Gly475Asp) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000137 in 1,461,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. G475V) has been classified as Uncertain significance.
Frequency
Consequence
NM_000642.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AGL | NM_000642.3 | c.1424G>A | p.Gly475Asp | missense_variant, splice_region_variant | 12/34 | ENST00000361915.8 | NP_000633.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AGL | ENST00000361915.8 | c.1424G>A | p.Gly475Asp | missense_variant, splice_region_variant | 12/34 | 1 | NM_000642.3 | ENSP00000355106.3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251184Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135750
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461590Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727094
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Glycogen storage disease type III Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 15, 2022 | 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. 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. This variant has not been reported in the literature in individuals affected with AGL-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 475 of the AGL protein (p.Gly475Asp). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at