rs1079348

Positions:

• chr16-8779599-T-C
• chr16-8779599-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020686.6(ABAT):​c.1381+9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,608,896 control chromosomes in the GnomAD database, including 73,976 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (8679 hom., cov: 32)
  • Exomes 𝑓: 0.30 (65297 hom.)
• Consequence: ABAT NM_020686.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.981

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-8779599-T-C is Benign according to our data. Variant chr16-8779599-T-C is described in ClinVar as [Benign]. Clinvar id is 321090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABAT	NM_020686.6	c.1381+9T>C		intron_variant		ENST00000268251.13	NP_065737.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABAT	ENST00000268251.13	c.1381+9T>C		intron_variant		1	NM_020686.6	ENSP00000268251.8

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50168 AN: 151830 Hom.: 8664 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.333

GnomAD3 exomes AF: 0.298 AC: 74451 AN: 249872 Hom.: 11537 AF XY: 0.301 AC XY: 40746 AN XY: 135176

Gnomad AFR exome AF: 0.438

Gnomad AMR exome AF: 0.228

Gnomad ASJ exome AF: 0.311

Gnomad EAS exome AF: 0.352

Gnomad SAS exome AF: 0.343

Gnomad FIN exome AF: 0.231

Gnomad NFE exome AF: 0.290

Gnomad OTH exome AF: 0.294

GnomAD4 exome AF: 0.296 AC: 431751 AN: 1456948 Hom.: 65297 Cov.: 30 AF XY: 0.299 AC XY: 216492 AN XY: 725150

Gnomad4 AFR exome AF: 0.436

Gnomad4 AMR exome AF: 0.234

Gnomad4 ASJ exome AF: 0.307

Gnomad4 EAS exome AF: 0.349

Gnomad4 SAS exome AF: 0.343

Gnomad4 FIN exome AF: 0.232

Gnomad4 NFE exome AF: 0.291

Gnomad4 OTH exome AF: 0.305

GnomAD4 genome AF: 0.331 AC: 50227 AN: 151948 Hom.: 8679 Cov.: 32 AF XY: 0.330 AC XY: 24533 AN XY: 74296

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.335

Alfa AF: 0.305 Hom.: 5318

Bravo AF: 0.338

Asia WGS AF: 0.352 AC: 1223 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Gamma-aminobutyric acid transaminase deficiency Benign:3

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	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

not provided Benign:3

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 11, 2016	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.52
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs1079348; hg19: chr16-8873456; COSMIC: COSV51623669; COSMIC: COSV51623669;