ClinVar Miner

Submissions for variant NM_000520.6(HEXA):c.1435G>A (p.Ala479Thr) (rs145012038)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000384004 SCV000340739 benign not specified 2016-04-15 criteria provided, single submitter clinical testing
Counsyl RCV000505691 SCV000599896 likely benign Tay-Sachs disease 2017-08-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000384004 SCV000919504 likely benign not specified 2018-04-09 criteria provided, single submitter clinical testing Variant summary: HEXA c.1435G>A (p.Ala479Thr) results in a non-conservative amino acid change located in the Glycoside hydrolase family 20, catalytic domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00082 in 277154 control chromosomes, predominantly at a frequency of 0.0084 within the East Asian subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 6.011 fold of the estimated maximal expected allele frequency for a pathogenic variant in HEXA causing Tay-Sachs Disease phenotype (0.0014), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. c.1435G>A has been reported in the literature , without strong evidence for causality (Strom_2013). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. One of these labs also published an abstract in which they tested 4-5 patient samples for the variant of interest and found HexA enzyme analysis to show negative Tay-Sachs carrier state for all subjects (Counsyl abstract from Molecular Genetics and Metabolism, 2018). Based on the evidence outlined above, the variant was classified as likely benign.
Invitae RCV000862163 SCV001002628 benign not provided 2019-03-04 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000862163 SCV001149514 uncertain significance not provided 2018-03-01 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.