owencqueen/cgbench_data huggingface dataset:
Gene: UBE3A (HGNC:12496)
Evidence Code: PVS1 — Very Strong
Modification Type: Disease-specific
Null variant in a gene where loss of function is a known mechanism of disease.




Use as defined by ClinGen SVI working group (PMID:30192042).


PVS1 is applicable for any truncating variant up to p.K841
5
, for any frameshift variant that results in a read-through of the stop codon, for initiation codon variants, for canonical splice site variants predicted to result in an out-of-frame product, and for intragenic deletions/duplications predicted to result in an out-of-frame product.
Gene: UBE3A (HGNC:12496)
Evidence Code: PS3 — Strong
Modification Type: Disease-specific
Well-established in vitro or in vivo functional studies supportive of a damaging effect.




RNA studies that demonstrate abnormal splicing and an out-of-frame transcript.


Do not use for canonical splice site variants and when PVS1 is used.
Gene: UBE3A (HGNC:12496)
Evidence Code: PM1 — Moderate
Modification Type: Disease-specific
Located in a mutational hot spot and/or critical and well-established functional domain.




3’ cysteine binding site: aa 820
5
Gene: UBE3A (HGNC:12496)
Evidence Code: PM4 — Strong
Modification Type: Disease-specific
Protein length changes due to stop-loss variants.




PM4_Strong is applicable to stop-loss variants in UBE3A, as several stop loss variants in this gene has been described in affected individuals.
9
Gene: UBE3A (HGNC:12496)
Evidence Code: PM4 — Moderate
Modification Type: Disease-specific
Protein length changes due to in-frame deletions/insertions in a non-repeat region.
Gene: UBE3A (HGNC:12496)
Evidence Code: PM5 — Moderate
Modification Type: None
Missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before.




A Grantham or BLOSUM score comparison can be used to determine if the variant is predicted to be as or more damaging than the established pathogenic variant.
Gene: UBE3A (HGNC:12496)
Evidence Code: PP3 — Supporting
Modification Type: General recommendation
Multiple lines of computational evidence support a deleterious effect on the gene or gene product.




For missense variants use REVEL with a score ≥ 0.75.


For splice site variants use MaxEntScan, NNSPLICE and SpliceSiteFinder-like when all of the prediction programs support significant splicing alteration (significant splicing alterations defined as ≥15% decrease to the natural splice site and ≥70% gain in prediction strength of cryptic splice site).
Gene: UBE3A (HGNC:12496)
Evidence Code: BA1 — Stand Alone
Modification Type: Disease-specific
Use large population databases (i.e. gnomAD).


Use if variant is present at ≥0.0003 (0.03%) in any sub-population.


Use if allele frequency is met in any general continental population dataset of at least 2,000 observed alleles.
Gene: UBE3A (HGNC:12496)
Evidence Code: BS1 — Strong
Modification Type: Disease-specific
Use large population databases (i.e. gnomAD).


Use if variant is present at ≥0.00008 (0.008%) and <0.0003 (0.03%) in any sub-population.


Use if allele frequency is met in any general continental population dataset of at least 2,000 observed alleles.
Gene: UBE3A (HGNC:12496)
Evidence Code: BS2 — Strong
Modification Type: Strength
Observed in the heterozygous/hemizygous state in a healthy adult.




4 unaffected (related and maternally inherited or unrelated) heterozygotes
Gene: UBE3A (HGNC:12496)
Evidence Code: BS2 — Supporting
Modification Type: Strength
Observed in the heterozygous/hemizygous state in a healthy adult.




2 unaffected (related and maternally inherited or unrelated) heterozygotes
Gene: UBE3A (HGNC:12496)
Evidence Code: BP2 — Supporting
Modification Type: Disease-specific
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.




BP2 is not applicable for UBE3A 
in trans
 state.
Gene: UBE3A (HGNC:12496)
Evidence Code: BP5 — Supporting
Modification Type: Disease-specific
Variant found in a case with an alternate molecular basis for disease.




1-2 cases with alternate molecular basis for disease.