Submissions for variant NM_004656.4(BAP1):c.1330A>G (p.Thr444Ala)

gnomAD frequency: 0.00027  dbSNP: rs374746213

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001079872	SCV000553969	likely benign	BAP1-related tumor predisposition syndrome	2024-01-30	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000503320	SCV000593577	uncertain significance	not specified	2017-05-30	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000771212	SCV000903250	likely benign	Hereditary cancer-predisposing syndrome	2016-06-27	criteria provided, single submitter	clinical testing
GeneDx	RCV000827317	SCV000968955	likely benign	not provided	2021-04-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000771212	SCV001171356	likely benign	Hereditary cancer-predisposing syndrome	2021-03-31	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital	RCV001079872	SCV002526062	uncertain significance	BAP1-related tumor predisposition syndrome	2022-05-12	criteria provided, single submitter	clinical testing	The BAP1 c.1330A>G (p.Thr444Ala) missense change has a maximum subpopulation frequency of 0.096% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). It is predicted to have a benign effect on protein function (BP4), but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with BAP1-related conditions. Five individuals with this variant are reported in a database of women older than 70 years of age who have never had cancer (FLOSSIES, https://whi.color.com/). In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: BP4.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000827317	SCV004220432	likely benign	not provided	2023-01-25	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003902655	SCV004727694	likely benign	BAP1-related condition	2023-12-11	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).