ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.4914_4917del (p.Asn1638fs)

dbSNP: rs779366889
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
Counsyl RCV000664658 SCV000788658 pathogenic Alstrom syndrome 2017-03-22 criteria provided, single submitter clinical testing
Invitae RCV000664658 SCV001584345 pathogenic Alstrom syndrome 2024-01-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn1639Lysfs*4) in the ALMS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALMS1 are known to be pathogenic (PMID: 17594715). This variant is present in population databases (rs779366889, gnomAD 0.03%). This premature translational stop signal has been observed in individual(s) with Alstrom syndrome and/or cone-rod dystrophy (PMID: 25846608, 26992781). ClinVar contains an entry for this variant (Variation ID: 550038). For these reasons, this variant has been classified as Pathogenic.
3billion RCV000664658 SCV002572884 pathogenic Alstrom syndrome 2022-09-01 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). Frameshift variant is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant was found to in trans with other pathogenic variant (3billion dataset). The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000550038 / PMID: 25846608). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.

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.