Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_020686.6(ABAT):c.30G>A(p.Leu10Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00275 in 1,607,970 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
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]
Our verdict: Benign. The variant received -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
Variant 16-8735769-G-A is Benign according to our data. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8735769-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 281798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.86 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00202 (307/152256) while in subpopulation AMR AF = 0.00451 (69/15290). AF 95% confidence interval is 0.00366. There are 1 homozygotes in GnomAd4. There are 145 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
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Feb 02, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
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Jan 13, 2018
Illumina Laboratory Services, Illumina
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
not providedBenign:2
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Breakthrough Genomics, Breakthrough Genomics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:not provided
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Feb 01, 2025
CeGaT Center for Human Genetics Tuebingen
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
ABAT: BP4, BP7, BS2 -
not specifiedBenign:1
Jun 30, 2015
Eurofins Ntd Llc (ga)
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
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ABAT-related disorderBenign:1
Mar 21, 2019
PreventionGenetics, part of Exact Sciences
Significance:Likely benign
Review Status:no assertion criteria provided
Collection Method:clinical testing
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -