rs201409613
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_000152.5(GAA):c.1417G>A(p.Gly473Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,613,188 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. G473A) has been classified as Uncertain significance.
Frequency
Consequence
NM_000152.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GAA | NM_000152.5 | c.1417G>A | p.Gly473Ser | missense_variant | 9/20 | ENST00000302262.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GAA | ENST00000302262.8 | c.1417G>A | p.Gly473Ser | missense_variant | 9/20 | 1 | NM_000152.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152210Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248930Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135282
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1460862Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9AN XY: 726754
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152326Hom.: 0 Cov.: 34 AF XY: 0.0000671 AC XY: 5AN XY: 74482
ClinVar
Submissions by phenotype
Glycogen storage disease, type II Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 18, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 04, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 473 of the GAA protein (p.Gly473Ser). This variant is present in population databases (rs201409613, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with GAA-related conditions. ClinVar contains an entry for this variant (Variation ID: 456377). 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 GAA 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at