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
3


Any frameshift variant that results in a read-through of the stop codon


Initiation codon variants


Canonical splice site variants predicted to result in an out-of-frame product


Intragenic deletions/duplications predicted to result in an out-of-frame product.


Full gene deletion
Gene: UBE3A (HGNC:12496)
Evidence Code: PVS1 — Strong
Modification Type: Disease-specific,Strength
Null variant in a gene where loss of function is a known mechanism of disease.




PVS1_Strong is applicable for:


Any truncating variant from p.A842 to p.G850 


Canonical splice site variants that flank exons 7, 8 (in-frame exons)
Gene: UBE3A (HGNC:12496)
Evidence Code: PVS1 — Moderate
Modification Type: Disease-specific,Strength
Null variant in a gene where loss of function is a known mechanism of disease.




PVS1_Moderate is applicable for any truncating variant distal of p.G850.
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
3
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.
4
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 ≥ 0.644.


For splice site variants use SpliceAI with a score ≥ 0.2.
Gene: UBE3A (HGNC:12496)
Evidence Code: BS2 — Moderate
Modification Type: Strength
Observed in the heterozygous/hemizygous state in a healthy adult.




3 unaffected (related and maternally inherited or unrelated) heterozygotes
Gene: UBE3A (HGNC:12496)
Evidence Code: BS3 — Strong
Modification Type: Disease-specific
Well-established in vitro or in vivo functional studies shows no damaging effect on protein function.




RNA functional studies that demonstrate no impact on splicing and transcript composition. It can be downgraded based on quality of data.


Not applicable for other functional studies.
Gene: UBE3A (HGNC:12496)
Evidence Code: BP3 — Supporting
Modification Type: None
In-frame deletions/insertions in a repetitive region without a known function.




BP3 is applicable if there are in-frame deletions/duplications in a repetitive region where other in-frame deletions/duplications have been observed with an overall frequency commensurate with the BA1 threshold for this gene.
Gene: UBE3A (HGNC:12496)
Evidence Code: BP4 — Supporting
Modification Type: None
Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc).




For missense variants use REVEL with a score ≤ 0.290.


For splice site variants use SpliceAI with a score ≤ 0.1.
Gene: UBE3A (HGNC:12496)
Evidence Code: BP5 — Moderate
Modification Type: Strength
Variant found in a case with an alternate molecular basis for disease. 




2 cases with alternate molecular basis for disease.
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 case with alternate molecular basis for disease.
Gene: UBE3A (HGNC:12496)
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.




Defined 'not highly conserved' regions in BP7 as those with PhastCons score <1 and/or PhyloP score <0.1 and/or the variant is the reference nucleotide in one primate and/or three mammal species.


For splice site variants use SpliceAI with a score ≤ 0.1.