rs375480247
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_ModerateBP6_ModerateBP7BS1
The NM_020686.6(ABAT):c.858G>A(p.Thr286=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,613,968 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000041 ( 0 hom. )
Consequence
ABAT
NM_020686.6 synonymous
NM_020686.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.663
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 -7 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
Variant 16-8772821-G-A is Benign according to our data. Variant chr16-8772821-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 529795.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.663 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0000789 (12/152094) while in subpopulation AFR AF= 0.000217 (9/41426). AF 95% confidence interval is 0.000113. There are 0 homozygotes in gnomad4. There are 6 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABAT | NM_020686.6 | c.858G>A | p.Thr286= | synonymous_variant | 12/16 | ENST00000268251.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABAT | ENST00000268251.13 | c.858G>A | p.Thr286= | synonymous_variant | 12/16 | 1 | NM_020686.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000789 AC: 12AN: 152094Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251466Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135914
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GnomAD4 exome AF: 0.0000410 AC: 60AN: 1461874Hom.: 0 Cov.: 32 AF XY: 0.0000426 AC XY: 31AN XY: 727236
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GnomAD4 genome ? AF: 0.0000789 AC: 12AN: 152094Hom.: 0 Cov.: 31 AF XY: 0.0000808 AC XY: 6AN XY: 74284
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Gamma-aminobutyric acid transaminase deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 25, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at