owencqueen/cgbench_data huggingface dataset:
Gene: GCK (HGNC:4195)
Evidence Code: PVS1 — Strong
Modification Type: Strength
Use 
GCK
 PVS1 decision tree.


Per the SVI standard PVS1 decision tree, apply PVS1_Strong to duplications ≥ 1 exon in size, contained completely within gene, presumed in tandem, reading frame presumed disrupted, and NMD predicted to occur.
Gene: GCK (HGNC:4195)
Evidence Code: PS1 — Supporting
Modification Type: Strength
PS1 may be used at a supporting level for canonical and non-canonical splicing variants when a different variant at the same nucleotide has been previously classified as pathogenic and the variant being assessed is predicted by SpliceAI to have a similar (SpliceAI score within 10% of the original variant) or greater deleterious impact.  For canonical splicing variants, PS1 may also be used at the supporting level if a variant at the other nucleotide in the same splice site has been previously classified as pathogenic and the variant being assessed is predicted by SpliceAI to have a similar (SpliceAI score within 10% of the original variant) or greater deleterious impact.
Gene: GCK (HGNC:4195)
Evidence Code: PM1 — Moderate
Modification Type: Gene-specific
Applicable for glucose- and ATP-binding sites (see attached chart for details).


Glucose-binding sites:  Ser151 - Pro153; Thr168 - Lys169;  Asn204 - Thr206; Ile225 - Asn231; Asn254 - Gly258; Gln287; Glu290


ATP-binding sites:  Asp78 - Arg85; Ser151; Lys169; Asp205; Ile225 - Gly229; Gly295 - Lys296; Glu331 - Arg333; Ser336; Gly410 - His416
Gene: GCK (HGNC:4195)
Evidence Code: PM2 — Supporting
Modification Type: Gene-specific
gnomAD v4.1 Grpmax FAF ≤ 1:333,000 (≤ 0.000003 or 0.0003%)
Gene: GCK (HGNC:4195)
Evidence Code: PM4 — Moderate
Modification Type: Strength
For deletions/insertions of more than one amino acid in a non-repeat region, use as moderate level of evidence.
Gene: GCK (HGNC:4195)
Evidence Code: PM4 — Supporting
Modification Type: Strength
Apply at the Supporting level when there is an insertion or deletion of a single amino acid in a non-repeat region.
Gene: GCK (HGNC:4195)
Evidence Code: PP4 — Moderate
Modification Type: Gene-specific,Strength
HbA1C 5.6 – 7.6% (38-60 mmol/mol) (if given multiple results, use maximum value) AND fasting plasma glucose always (FPG) 5.5-8 mmol/L (100-144 mg/dL) AND presence of any of the following additional features:




Pediatric patient (prepubertal or <10 years) (picked up in the absence of symptoms, either incidentally during workup for an unrelated indication or during routine screening)


Multiple values (=persistent) of mild fasting hyperglycemia in PP4 range


Either (≥ 1 HbA1c + ≥ 2 FPG) OR (≥ 2 HbA1c + ≥ 1 FPG)


Only 1 HbA1c and 1 FPG in range but they are at least 6 months apart


Patient in literature is described as having a multi-year history of impaired fasting glucose (IFG)






OGTT (oral glucose tolerance test) with 2-hour increment <3 mmol/L (54 mg/dl) 


Antibody negative 


Macrosomia in normoglycemic offspring of hyperglycemic gestational parent


Low birthweight in hyperglycemic offspring of hyperglycemic gestational parent. 


Three-generation, dominant family history of diabetes or hyperglycemia (in a family not used for PP1)
Gene: GCK (HGNC:4195)
Evidence Code: PP4 — Supporting
Modification Type: Gene-specific
HbA1C 5.6 – 7.6% (38-60 mmol/mol) (if given multiple results, use maximum value) AND fasting plasma glucose always (FPG) 5.5-8 mmol/L (100-144 mg/dL)
Gene: GCK (HGNC:4195)
Evidence Code: BA1 — Stand Alone
Modification Type: Gene-specific
gnomAD v4.1 Grpmax FAF ≥ 1:10,000 (≥ 0.01% or 0.0001)
Gene: GCK (HGNC:4195)
Evidence Code: BS1 — Strong
Modification Type: Gene-specific
gnomAD v4.1 Grpmax FAF ≥ 1:25,000 (0.004% or 0.00004)