rs200856561
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM5
The NM_000152.5(GAA):āc.752C>Gā(p.Ser251Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,108 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S251L) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000152.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GAA | NM_000152.5 | c.752C>G | p.Ser251Trp | missense_variant | 4/20 | ENST00000302262.8 | NP_000143.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GAA | ENST00000302262.8 | c.752C>G | p.Ser251Trp | missense_variant | 4/20 | 1 | NM_000152.5 | ENSP00000305692.3 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152200Hom.: 0 Cov.: 34
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460908Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 726784
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152200Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74346
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 24, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Glycogen storage disease, type II Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 27, 2022 | This sequence change replaces serine, which is neutral and polar, with tryptophan, which is neutral and slightly polar, at codon 251 of the GAA protein (p.Ser251Trp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GAA-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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