ClinVar Miner

Submissions for variant NM_003922.4(HERC1):c.9439G>A (p.Val3147Ile)

gnomAD frequency: 0.00051  dbSNP: rs200243610
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV001329792 SCV001521327 uncertain significance Macrocephaly, dysmorphic facies, and psychomotor retardation 2020-05-21 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp RCV002546353 SCV003492977 uncertain significance not provided 2022-06-10 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 3147 of the HERC1 protein (p.Val3147Ile). This variant is present in population databases (rs200243610, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with HERC1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1028683). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
GeneDx RCV002546353 SCV005419516 uncertain significance not provided 2025-04-08 criteria provided, single submitter clinical testing In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
PreventionGenetics, part of Exact Sciences RCV003953667 SCV004783400 likely benign HERC1-related disorder 2022-07-21 no assertion criteria provided clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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