NM_020686.6:c.30G>A

Variant names:

• chr16-8735769-G-A
• rs34813662
• NM_020686.6:c.30G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

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 (★★).

• Frequency:
  • Genomes: 𝑓 0.0020 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (15 hom.)
• Consequence: ABAT NM_020686.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 1.86
• Publications: 3 publications found

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]

ABAT Gene-Disease associations (from GenCC):

• GABA aminotransaminase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia, Orphanet, G2P
• genetic developmental and epileptic encephalopathy

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

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.
• BS2: High Homozygotes in GnomAdExome4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABAT	NM_020686.6	c.30G>A	p.Leu10Leu	synonymous_variant	Exon 2 of 16	ENST00000268251.13	NP_065737.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABAT	ENST00000268251.13	c.30G>A	p.Leu10Leu	synonymous_variant	Exon 2 of 16	1	NM_020686.6	ENSP00000268251.8

Frequencies

GnomAD3 genomes AF: 0.00202 AC: 307 AN: 152138 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00452

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00313

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00186 AC: 445 AN: 239294 AF XY: 0.00178

Gnomad AFR exome AF: 0.000663

Gnomad AMR exome AF: 0.00190

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000353

Gnomad NFE exome AF: 0.00324

Gnomad OTH exome AF: 0.00171

GnomAD4 exome AF: 0.00282 AC: 4110 AN: 1455714 Hom.: 15 Cov.: 31 AF XY: 0.00274 AC XY: 1985 AN XY: 723520

African (AFR) AF: 0.000418 AC: 14 AN: 33458

American (AMR) AF: 0.00209 AC: 92 AN: 44032

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25908

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.0000708 AC: 6 AN: 84722

European-Finnish (FIN) AF: 0.000762 AC: 40 AN: 52486

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00346 AC: 3835 AN: 1109536

Other (OTH) AF: 0.00204 AC: 123 AN: 60188

GnomAD4 genome AF: 0.00202 AC: 307 AN: 152256 Hom.: 1 Cov.: 32 AF XY: 0.00195 AC XY: 145 AN XY: 74450

African (AFR) AF: 0.000482 AC: 20 AN: 41530

American (AMR) AF: 0.00451 AC: 69 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00313 AC: 213 AN: 68030

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00231 Hom.: 1

Bravo AF: 0.00273

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Gamma-aminobutyric acid transaminase deficiency Benign:3

Nov 22, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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 provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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 specified Benign:1

Jun 30, 2015

Eurofins Ntd Llc (ga)

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

ABAT-related disorder Benign: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). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	3.0
DANN	Benign	0.62
PhyloP100		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34813662; hg19: chr16-8829626;