rs2228081
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_020686.6(ABAT):c.129G>A(p.Gly43=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00532 in 1,613,824 control chromosomes in the GnomAD database, including 390 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.028 ( 198 hom., cov: 31)
Exomes 𝑓: 0.0029 ( 192 hom. )
Consequence
ABAT
NM_020686.6 synonymous
NM_020686.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.526
Genes affected
ABAT (HGNC:23): (4-aminobutyrate aminotransferase) 4-aminobutyrate aminotransferase (ABAT) is responsible for catabolism of gamma-aminobutyric acid (GABA), an important, mostly inhibitory neurotransmitter in the central nervous system, into succinic semialdehyde. The active enzyme is a homodimer of 50-kD subunits complexed to pyridoxal-5-phosphate. The protein sequence is over 95% similar to the pig protein. GABA is estimated to be present in nearly one-third of human synapses. ABAT in liver and brain is controlled by 2 codominant alleles with a frequency in a Caucasian population of 0.56 and 0.44. The ABAT deficiency phenotype includes psychomotor retardation, hypotonia, hyperreflexia, lethargy, refractory seizures, and EEG abnormalities. Multiple alternatively spliced transcript variants encoding the same protein isoform have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
?
Variant 16-8746059-G-A is Benign according to our data. Variant chr16-8746059-G-A is described in ClinVar as [Benign]. Clinvar id is 320840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.526 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0969 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABAT | NM_020686.6 | c.129G>A | p.Gly43= | synonymous_variant | 3/16 | ENST00000268251.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABAT | ENST00000268251.13 | c.129G>A | p.Gly43= | synonymous_variant | 3/16 | 1 | NM_020686.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0284 AC: 4319AN: 152048Hom.: 198 Cov.: 31
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GnomAD3 exomes AF: 0.00736 AC: 1851AN: 251364Hom.: 82 AF XY: 0.00509 AC XY: 692AN XY: 135846
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GnomAD4 exome AF: 0.00291 AC: 4257AN: 1461658Hom.: 192 Cov.: 32 AF XY: 0.00243 AC XY: 1765AN XY: 727140
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GnomAD4 genome ? AF: 0.0284 AC: 4324AN: 152166Hom.: 198 Cov.: 31 AF XY: 0.0274 AC XY: 2042AN XY: 74400
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Gamma-aminobutyric acid transaminase deficiency Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:2
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Mar 16, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Aug 24, 2017 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at