ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.4153dup (p.Thr1385fs)

gnomAD frequency: 0.00002  dbSNP: rs797045228
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000194605 SCV000246358 pathogenic Alstrom syndrome 2014-05-06 criteria provided, single submitter clinical testing
Counsyl RCV000194605 SCV000790750 pathogenic Alstrom syndrome 2017-04-06 criteria provided, single submitter clinical testing
Invitae RCV000194605 SCV000950098 pathogenic Alstrom syndrome 2023-10-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr1386Asnfs*15) 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 (rs757011587, gnomAD 0.005%). This premature translational stop signal has been observed in individual(s) with Alstrom syndrome (PMID: 23188138, 25296579, 25706677, 28432734). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 210127). For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV001091464 SCV001247528 pathogenic not provided 2018-08-01 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001091464 SCV001447537 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV000194605 SCV002768854 pathogenic Alstrom syndrome 2020-05-21 criteria provided, single submitter clinical testing A heterozygous duplication variant was identified, NM_015120.4(ALMS1):c.4156dupA in exon 8 of 23 of the ALMS1 gene. This duplication is predicted to cause a frameshift from amino acid position 1386 introducing a stop codon downstream; NP_055935.4(ALMS1):p.(Thr1386Asnfs*15), resulting in loss of normal protein function through nonsense-mediated decay (NMD). The variant is present in the gnomAD population database at a global population frequency of 0.0021% (6 heterozygotes, 0 homozygotes), with a European sub-population frequency of 0.0047%. The variant has been previously reported in patients with Alstrom syndrome (ClinVar, Dotan, G. et al. (2017)). Other variants predicted to cause NMD have been reported as pathogenic in individuals with Alstrom syndrome (ClinVar, Marshall, J. D. et al. (2007)). Based on information available at the time of curation, this variant has been classified as PATHOGENIC.
Laboratory of Genetics in Ophthalmology, Institut Imagine RCV000194605 SCV001432510 pathogenic Alstrom syndrome no assertion criteria provided research
Natera, Inc. RCV000194605 SCV002080499 pathogenic Alstrom syndrome 2020-09-10 no assertion criteria provided clinical testing

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