ClinVar Miner

Submissions for variant NM_005334.3(HCFC1):c.3730C>T (p.Arg1244Cys)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
New York Genome Center RCV001291690 SCV001480272 uncertain significance Mental retardation 3, X-linked 2019-10-05 criteria provided, single submitter clinical testing The hemizyous, maternally inherited c.3730C>T (p.Arg1244Cys) variant identified in the HCFC1 gene substitutes a completely conserved Arginine for Cysteine at amino acid 1244/2036 (coding exon 17/26).This variant is found with low frequency in gnomAD (4 heterozygotes, 0 homozygoes, 0 hemizygotes; allele frequency: 2.412e-5) and ExAC (2 heterozygotes, 0 homozygotes, 0 hemizygotes; allele frequency: 3.165e-5), suggesting it is not a common benign variant in the populations represented in these databases. This variant is absent from ClinVar and to our current knowledge has not been reported in affected individuals in the literature. In silico algorithms do not predict this variant is damaging to the function of the canonical transcript, as it is predicted Neutral (Provean; score: -1.79) and Tolerated (SIFT; score: 0.083). The p.Arg1244 reside is within the HCF-proteolysis repeat domain of HCFC1, which is not enriched in pathogenic variants. Given the lack of compelling information regarding its pathogenicity, the c.3730C>T (p.Arg1244Cys) variant identified in the HCFC1 gene is reported here as a Variant of Uncertain Significance.

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