ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.12442C>T (p.Arg4148Ter)

gnomAD frequency: 0.00002  dbSNP: rs192496253
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668094 SCV000792642 uncertain significance Alstrom syndrome 2017-07-06 criteria provided, single submitter clinical testing
GeneDx RCV001584538 SCV001819984 uncertain significance not provided 2020-12-08 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation as the last 21 amino acids are lost, although loss-of-function variants have not been reported downstream of this position in the protein; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV000668094 SCV002110129 uncertain significance Alstrom syndrome 2022-06-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg4149*) in the ALMS1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 21 amino acid(s) of the ALMS1 protein. This variant is present in population databases (rs192496253, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with ALMS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 552771). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV002388179 SCV002671720 uncertain significance Cardiovascular phenotype 2021-07-06 criteria provided, single submitter clinical testing The p.R4149* variant (also known as c.12445C>T), located in coding exon 22 of the ALMS1 gene, results from a C to T substitution at nucleotide position 12445. This changes the amino acid from an arginine to a stop codon within coding exon 22. This alteration occurs at the 3' terminus of theALMS1 gene, is not expected to trigger nonsense-mediated mRNAdecay, and only impacts the last 21 amino acids of the protein. The exact functional effect of this alteration is unknown. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV000668094 SCV002788412 uncertain significance Alstrom syndrome 2021-10-27 criteria provided, single submitter clinical testing
Natera, Inc. RCV000668094 SCV002081418 uncertain significance Alstrom syndrome 2021-06-10 no assertion criteria provided clinical testing

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