16-8781314-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PVS1_ModeratePM2BS1_Supporting
The NM_001386616.1(ABAT):c.1446G>A(p.Trp482*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,614,132 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_001386616.1 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251420Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135892
GnomAD4 exome AF: 0.0000287 AC: 42AN: 1461830Hom.: 0 Cov.: 34 AF XY: 0.0000426 AC XY: 31AN XY: 727218
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152302Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1AN XY: 74468
ClinVar
Submissions by phenotype
Gamma-aminobutyric acid transaminase deficiency Uncertain:1
This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 463 of the ABAT protein (p.Val463Met). This variant is present in population databases (rs757912430, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with ABAT-related conditions. ClinVar contains an entry for this variant (Variation ID: 1016313). 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 methionine 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at