16-8760130-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020686.6(ABAT):c.366+2324T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 152,148 control chromosomes in the GnomAD database, including 44,005 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.76 (43985 hom., cov: 32)
  • Exomes 𝑓: 0.87 (20 hom.)
• Consequence: ABAT NM_020686.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABAT	NM_020686.6	c.366+2324T>C		intron_variant		ENST00000268251.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABAT	ENST00000268251.13	c.366+2324T>C		intron_variant		1	NM_020686.6	P1

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115438 AN: 151978 Hom.: 43958 Cov.: 32

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.740

GnomAD4 exome AF: 0.865 AC: 45 AN: 52 Hom.: 20 Cov.: 0 AF XY: 0.800 AC XY: 24 AN XY: 30

Gnomad4 ASJ exome AF: 1.00

Gnomad4 FIN exome AF: 0.893

Gnomad4 NFE exome AF: 0.750

Gnomad4 OTH exome AF: 0.900

GnomAD4 genome AF: 0.759 AC: 115513 AN: 152096 Hom.: 43985 Cov.: 32 AF XY: 0.758 AC XY: 56335 AN XY: 74346

Gnomad4 AFR AF: 0.711

Gnomad4 AMR AF: 0.796

Gnomad4 ASJ AF: 0.738

Gnomad4 EAS AF: 0.821

Gnomad4 SAS AF: 0.690

Gnomad4 FIN AF: 0.799

Gnomad4 NFE AF: 0.777

Gnomad4 OTH AF: 0.742

Alfa AF: 0.769 Hom.: 93627

Bravo AF: 0.757

Asia WGS AF: 0.780 AC: 2712 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.5
Dann	Benign	0.49

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: rs8046201; hg19: chr16-8853987;