ClinVar Miner

Submissions for variant NM_183235.3(RAB27A):c.518C>G (p.Ala173Gly)

gnomAD frequency: 0.00011  dbSNP: rs142217102
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000823371 SCV000964226 uncertain significance Griscelli syndrome type 2 2022-07-06 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 173 of the RAB27A protein (p.Ala173Gly). This variant is present in population databases (rs142217102, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with RAB27A-related conditions. ClinVar contains an entry for this variant (Variation ID: 665149). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RAB27A 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.
PreventionGenetics, part of Exact Sciences RCV003424365 SCV004117756 uncertain significance RAB27A-related disorder 2023-08-27 criteria provided, single submitter clinical testing The RAB27A c.518C>G variant is predicted to result in the amino acid substitution p.Ala173Gly. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/15-55497853-G-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004586952 SCV005076112 uncertain significance not specified 2024-04-16 criteria provided, single submitter clinical testing Variant summary: RAB27A c.518C>G (p.Ala173Gly) results in a non-conservative amino acid change located in the Small GTP-binding protein domain (IPR005225) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6.4e-05 in 251052 control chromosomes. c.518C>G has been reported in the literature at a heterozygous status in a family with Left Ventricular Noncompaction, and did not segregate with disease (Bainbridge_2015). These report(s) do not provide unequivocal conclusions about association of the variant with Griscelli Syndrome Type 2. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 26025024). ClinVar contains an entry for this variant (Variation ID: 665149). Based on the evidence outlined above, the variant was classified as uncertain significance.

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