ClinVar Miner

Submissions for variant NM_005245.4(FAT1):c.3874G>A (p.Glu1292Lys)

gnomAD frequency: 0.00051  dbSNP: rs184443677
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000960848 SCV001107874 benign not provided 2024-01-12 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003935933 SCV004751749 benign FAT1-related condition 2022-11-30 criteria provided, single submitter clinical testing This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000960848 SCV001549082 likely benign not provided no assertion criteria provided clinical testing The FAT1 p.Glu1292Lys variant was not identified in the literature nor was it identified in ClinVar, Cosmic, or LOVD 3.0. The variant was identified in dbSNP (ID: rs184443677) and in control databases in 226 of 280594 chromosomes at a frequency of 0.000805 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: East Asian in 203 of 19530 chromosomes (freq: 0.01039), Other in 6 of 7138 chromosomes (freq: 0.000841), Latino in 7 of 35370 chromosomes (freq: 0.000198), South Asian in 6 of 30602 chromosomes (freq: 0.000196), African in 3 of 24176 chromosomes (freq: 0.000124) and European (non-Finnish) in 1 of 128406 chromosomes (freq: 0.000008), but was not observed in the Ashkenazi Jewish or European (Finnish) populations. The p.Glu1292 residue is conserved across mammals and other organisms, and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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.