ClinVar Miner

Submissions for variant NM_015120.4(ALMS1):c.12428A>G (p.Tyr4143Cys) (rs775032572)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000485128 SCV000574391 uncertain significance not provided 2018-03-21 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ALMS1 gene. The Y4143C variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). This variant may be functionally significant at the protein level or the mRNA level. At the protein level, the Y4143C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Moreover, in-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. At the mRNA level, in silico splice prediction programs predict that the c.12428 A>G variant creates a strong cryptic splice donor site upstream of the canonical splice donor site in intron 22, which may lead to abnormal gene splicing. However, in the absence of functional mRNA studies, the physiological consequences of the c.12428 A>G variant cannot be precisely determined.

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