ClinVar Miner

Submissions for variant NM_019109.5(ALG1):c.821G>A (p.Arg274His)

gnomAD frequency: 0.00003  dbSNP: rs529013891
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002070224 SCV002336572 benign ALG1-congenital disorder of glycosylation 2024-01-24 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001354787 SCV001549485 likely benign not provided no assertion criteria provided clinical testing The ALG1 p.Arg274His variant was not identified in the literature nor was it identified in ClinVar. The variant was identified in dbSNP (ID: rs529013891) and in control databases in 166 of 280372 chromosomes (1 homozygous) at a frequency of 0.0005921 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: South Asian in 159 of 30600 chromosomes (freq: 0.005196), Other in 2 of 7170 chromosomes (freq: 0.000279), East Asian in 1 of 19932 chromosomes (freq: 0.00005) and European (non-Finnish) in 4 of 127584 chromosomes (freq: 0.000031), but was not observed in the African, Latino, Ashkenazi Jewish, or European (Finnish) populations. The p.Arg274 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out 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) predict a greater than 10% difference in splicing. However, this information is not predictive enough to assume pathogenicity. 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.