16-8781357-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_020686.6(ABAT):c.1430C>T(p.Thr477Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000719 in 1,614,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T477A) has been classified as Uncertain significance.
Frequency
Consequence
NM_020686.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABAT | NM_020686.6 | c.1430C>T | p.Thr477Met | missense_variant | 16/16 | ENST00000268251.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABAT | ENST00000268251.13 | c.1430C>T | p.Thr477Met | missense_variant | 16/16 | 1 | NM_020686.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152128Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251480Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135912
GnomAD4 exome AF: 0.0000725 AC: 106AN: 1461886Hom.: 0 Cov.: 33 AF XY: 0.0000619 AC XY: 45AN XY: 727246
GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152128Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3AN XY: 74316
ClinVar
Submissions by phenotype
Gamma-aminobutyric acid transaminase deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 29, 2022 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 477 of the ABAT protein (p.Thr477Met). This variant is present in population databases (rs778305265, gnomAD 0.007%). 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: 959766). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; 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