owencqueen/cgbench_data huggingface dataset:
Gene: GAMT (HGNC:4136)
Evidence Code: BS3 — Supporting
Modification Type: Strength,Disease-specific
30% normal GAA activity when the variant is expressed in a heterologous cell type.
GAMT specifications:
In vitro assays in which a variant is expressed in GAMT-deficient cultured cells (e.g. GAMT-deficient fibroblasts) or in-fusion High-Fidelity cloning of GAMT transcript and site directed mutagenesis to generate missense variant overexpressed in HeLa cells and measurement of GAMT activity in cells for wild-type and missense variant. Any variant with enzyme activity at or above 30% of normal in the following publications meets BS3_Supporting (Mercimek-Mahmutoglu et al, 2014; PMID 24415674; Mercimek-Mahmutoglu et al, 2016, PMID 26319512; DesRoches et al, 2016, PMID 26003046).
Gene: GAMT (HGNC:4136)
Evidence Code: BP2 — Supporting
Modification Type: None
Observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder; or observed in cis with a pathogenic variant in any inheritance pattern.
GAMT specifications:
Observed in cis with a pathogenic variant (to take AR inheritance into account).
Gene: GAMT (HGNC:4136)
Evidence Code: BP4 — Supporting
Modification Type: None
GAMT specifications:




For missense changes, REVEL score <0.5.


For in frame insertions and deletions, use PROVEAN and Mutation Taster. Results must be consistent to count.


For non-canonical splice site variants, use SpliceAI (
https://spliceailookup.broadinstitute.org/
 ) and varSEAK (
https://varseak.bio/
) to assess the impact of variants that are not +/-1 or 2 canonical splice site variants. For SpliceAI, this criterion can be applied for scores <0.2, and for varSEAK class 1 and 2. If there is any evidence for possible creation of a cryptic splice site, this criterion should not be applied.
Gene: GAMT (HGNC:4136)
Evidence Code: BP7 — Supporting
Modification Type: None
A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved.
GAMT specifications:
Apply this criterion as described.