16-8781189-TGATG-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_020686.6(ABAT):c.1382-95_1382-92del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 1,429,434 control chromosomes in the GnomAD database, including 290,281 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.61 (28050 hom., cov: 0)
  • Exomes 𝑓: 0.64 (262231 hom.)
• Consequence: ABAT NM_020686.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00100

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]

TMEM186 (HGNC:24530): (transmembrane protein 186) This gene encodes a potential transmembrane protein. [provided by RefSeq, Dec 2012]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 16-8781189-TGATG-T is Benign according to our data. Variant chr16-8781189-TGATG-T is described in ClinVar as [Benign]. Clinvar id is 1185367.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABAT	NM_020686.6	c.1382-95_1382-92del		intron_variant		ENST00000268251.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABAT	ENST00000268251.13	c.1382-95_1382-92del		intron_variant		1	NM_020686.6	P1

Frequencies

GnomAD3 genomes AF: 0.607 AC: 91327 AN: 150518 Hom.: 28049 Cov.: 0

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.713

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.622

GnomAD4 exome AF: 0.640 AC: 818481 AN: 1278800 Hom.: 262231 AF XY: 0.639 AC XY: 412509 AN XY: 645186

Gnomad4 AFR exome AF: 0.485

Gnomad4 AMR exome AF: 0.576

Gnomad4 ASJ exome AF: 0.695

Gnomad4 EAS exome AF: 0.651

Gnomad4 SAS exome AF: 0.592

Gnomad4 FIN exome AF: 0.671

Gnomad4 NFE exome AF: 0.649

Gnomad4 OTH exome AF: 0.635

GnomAD4 genome AF: 0.606 AC: 91352 AN: 150634 Hom.: 28050 Cov.: 0 AF XY: 0.603 AC XY: 44336 AN XY: 73534

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.709

Gnomad4 EAS AF: 0.631

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.667

Gnomad4 NFE AF: 0.663

Gnomad4 OTH AF: 0.620

Bravo AF: 0.598

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Gamma-aminobutyric acid transaminase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

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Computational scores

Source: dbNSFP v4.3

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: rs3217123; hg19: chr16-8875046;