rs138812846
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_000152.5(GAA):c.32G>A(p.Arg11Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000942 in 1,612,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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. R11G) 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_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GAA | NM_000152.5 | c.32G>A | p.Arg11Gln | missense_variant | 2/20 | ENST00000302262.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GAA | ENST00000302262.8 | c.32G>A | p.Arg11Gln | missense_variant | 2/20 | 1 | NM_000152.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000309 AC: 47AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000124 AC: 31AN: 249320Hom.: 0 AF XY: 0.0000960 AC XY: 13AN XY: 135356
GnomAD4 exome AF: 0.0000692 AC: 101AN: 1460462Hom.: 0 Cov.: 31 AF XY: 0.0000647 AC XY: 47AN XY: 726558
GnomAD4 genome ? AF: 0.000335 AC: 51AN: 152296Hom.: 0 Cov.: 32 AF XY: 0.000403 AC XY: 30AN XY: 74464
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 07, 2015 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Sep 07, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 28, 2020 | This variant is associated with the following publications: (PMID: 18425781, 31301153) - |
not specified Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | May 25, 2018 | Variant summary: GAA c.32G>A (p.Arg11Gln) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00014 in 275638 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in GAA causing Glycogen Storage Disease, Type 2 (Pompe Disease) (0.00014 vs 0.0042), allowing no conclusion about variant significance. The variant, c.32G>A, has been reported in the literature in individuals affected with Glycogen Storage Disease, Type 2 (Pompe Disease)(Kroos_2008) but was classified as not pathogenic by the authors. These report(s) do not provide unequivocal conclusions about association of the variant with Glycogen Storage Disease, Type 2 (Pompe Disease). At least one publication reports experimental evidence evaluating an impact on protein function. These results showed no damaging effect of this variant (Kroos_2008). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (likely benign x1, uncertain significance 2x). Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Glycogen storage disease, type II Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at