rs757760608
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The ENST00000336787.6(RAB27A):c.526A>T(p.Met176Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,614,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
ENST00000336787.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RAB27A | NM_183235.3 | c.526A>T | p.Met176Leu | missense_variant | 7/7 | ENST00000336787.6 | NP_899058.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RAB27A | ENST00000336787.6 | c.526A>T | p.Met176Leu | missense_variant | 7/7 | 1 | NM_183235.3 | ENSP00000337761 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251206Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135814
GnomAD4 exome AF: 0.000120 AC: 175AN: 1461850Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 88AN XY: 727236
GnomAD4 genome AF: 0.0000723 AC: 11AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74334
ClinVar
Submissions by phenotype
Griscelli syndrome type 2 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 12, 2024 | This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 176 of the RAB27A protein (p.Met176Leu). This variant is present in population databases (rs757760608, gnomAD 0.005%). 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: 316647). 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 with a negative predictive value of 95%. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at