3-81490409-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_000158.4(GBE1):āc.2107T>Gā(p.Ter703Glyext*?) variant causes a stop lost change. The variant allele was found at a frequency of 0.00000658 in 152,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_000158.4 stop_lost
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152066Hom.: 0 Cov.: 32
GnomAD4 exome Cov.: 29
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152066Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74266
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant summary: GBE1 c.2107T>G (p.X703GlyextX25) changes the termination codon and is predicted to lead to an extended protein with additional amino acids added to the normal C-terminus. GBE1 c.2107T>G (p.X703GlyextX25) causes a frameshift which results in an extension of the protein. The variant was absent in 248702 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2107T>G in individuals affected with Glycogen Storage Disease, Type IV and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. -
not provided Uncertain:1
Not observed in large population cohorts (Lek et al., 2016); Normal stop codon changed to a Gly codon, leading to the addition of 25 amino acids at the C-terminus; Has not been previously published as pathogenic or benign to our knowledge -
Glycogen storage disease, type IV;C1856301:Glycogen storage disease IV, classic hepatic Uncertain:1
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. ClinVar contains an entry for this variant (Variation ID: 1304929). This variant has not been reported in the literature in individuals affected with GBE1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change disrupts the translational stop signal of the GBE1 mRNA. It is expected to extend the length of the GBE1 protein by 25 additional amino acid residues. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at