ClinVar Miner

Submissions for variant NM_005334.3(HCFC1):c.2626G>A (p.Gly876Ser) (rs200053475)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000487553 SCV000575666 uncertain significance not provided 2017-01-01 criteria provided, single submitter clinical testing
GeneDx RCV000487553 SCV000969535 likely benign not provided 2017-09-26 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV001247405 SCV001420825 uncertain significance Mental retardation 3, X-linked 2019-04-12 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 876 of the HCFC1 protein (p.Gly876Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs200053475, ExAC 0.06%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been observed in multiple individuals affected with HCFC1-related conditions (PMID: 23000143, 25740848). ClinVar contains an entry for this variant (Variation ID: 425515). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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