Submissions for variant NM_183235.3(RAB27A):c.307A>G (p.Asn103Asp)

gnomAD frequency: 0.00013  dbSNP: rs144492641

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001116408	SCV001274479	uncertain significance	Griscelli syndrome type 2	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Invitae	RCV001116408	SCV001412097	uncertain significance	Griscelli syndrome type 2	2022-08-23	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 103 of the RAB27A protein (p.Asn103Asp). This variant is present in population databases (rs144492641, gnomAD 0.03%). 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: 885036). 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 not expected to disrupt RAB27A protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002264191	SCV002542924	uncertain significance	Autoinflammatory syndrome	2021-08-09	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002558151	SCV003705502	uncertain significance	Inborn genetic diseases	2021-08-13	criteria provided, single submitter	clinical testing	The c.307A>G (p.N103D) alteration is located in exon 4 (coding exon 3) of the RAB27A gene. This alteration results from a A to G substitution at nucleotide position 307, causing the asparagine (N) at amino acid position 103 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.