ClinVar Miner

Submissions for variant NM_005245.4(FAT1):c.13727C>T (p.Thr4576Met)

gnomAD frequency: 0.01074  dbSNP: rs142057401
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
Labcorp Genetics (formerly Invitae), Labcorp RCV000964926 SCV001112176 benign not provided 2025-01-20 criteria provided, single submitter clinical testing
GeneDx RCV000964926 SCV001772733 likely benign not provided 2021-05-04 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001358120 SCV001553774 benign not specified no assertion criteria provided clinical testing The FAT1 p.Thr4576Met variant was not identified in the literature nor was it identified in LOVD 3.0 or Cosmic. The variant was identified in dbSNP (ID: rs142057401) and ClinVar (classified as benign by Invitae). The variant was identified in control databases in 948 of 279736 chromosomes (11 homozygous) at a frequency of 0.003389 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: African in 854 of 24180 chromosomes (freq: 0.03532), Latino in 58 of 35310 chromosomes (freq: 0.001643), Other in 6 of 7116 chromosomes (freq: 0.000843), European (non-Finnish) in 24 of 127842 chromosomes (freq: 0.000188), East Asian in 3 of 19516 chromosomes (freq: 0.000154) and South Asian in 3 of 30556 chromosomes (freq: 0.000098), but was not observed in the Ashkenazi Jewish or European (Finnish) populations. The p.Thr4576 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and three of four 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 this variant meets our laboratory's criteria to be classified as 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.