chr4-13369953-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_004249.4(RAB28):c.586G>A(p.Ala196Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000354 in 1,611,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_004249.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RAB28 | NM_004249.4 | c.586G>A | p.Ala196Thr | missense_variant | Exon 7 of 8 | ENST00000288723.9 | NP_004240.2 | |
RAB28 | NM_001017979.3 | c.574-1303G>A | intron_variant | Intron 6 of 6 | ENST00000330852.10 | NP_001017979.1 | ||
RAB28 | NM_001159601.2 | c.*32-1303G>A | intron_variant | Intron 7 of 7 | NP_001153073.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RAB28 | ENST00000288723.9 | c.586G>A | p.Ala196Thr | missense_variant | Exon 7 of 8 | 1 | NM_004249.4 | ENSP00000288723.4 | ||
RAB28 | ENST00000330852.10 | c.574-1303G>A | intron_variant | Intron 6 of 6 | 1 | NM_001017979.3 | ENSP00000328551.5 |
Frequencies
GnomAD3 genomes AF: 0.0000727 AC: 11AN: 151272Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000879 AC: 22AN: 250310Hom.: 0 AF XY: 0.0000887 AC XY: 12AN XY: 135338
GnomAD4 exome AF: 0.0000315 AC: 46AN: 1459916Hom.: 0 Cov.: 30 AF XY: 0.0000344 AC XY: 25AN XY: 726266
GnomAD4 genome AF: 0.0000727 AC: 11AN: 151272Hom.: 0 Cov.: 32 AF XY: 0.0000407 AC XY: 3AN XY: 73788
ClinVar
Submissions by phenotype
not provided Uncertain:1
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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with RAB28-related conditions. This variant is present in population databases (rs201945581, ExAC 0.06%). This sequence change replaces alanine with threonine at codon 196 of the RAB28 protein (p.Ala196Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at