ClinVar Miner

Submissions for variant NM_001830.4(CLCN4):c.10G>T (p.Ala4Ser)

gnomAD frequency: 0.00001  dbSNP: rs1015209935
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000767936 SCV000898614 uncertain significance Intellectual disability, X-linked 49 2021-03-30 criteria provided, single submitter clinical testing CLCN4 NM_001830 exon 3 p.Ala4Ser (c.10G>T): This variant has not been reported in the literature but is present in 1/25980 Latino individuals in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs not available). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV001321811 SCV001512660 uncertain significance not provided 2020-10-12 criteria provided, single submitter clinical testing This sequence change replaces alanine with serine at codon 4 of the CLCN4 protein (p.Ala4Ser). The alanine residue is weakly conserved and there is a moderate physicochemical difference between alanine and serine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CLCN4-related conditions. ClinVar contains an entry for this variant (Variation ID: 625920). This variant is not present in population databases (ExAC no frequency).

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