NM_020686.6:c.-42+12454G>C

Variant names:

• chr16-8687165-G-C
• rs1273350
• NM_020686.6:c.-42+12454G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020686.6(ABAT):​c.-42+12454G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 151,970 control chromosomes in the GnomAD database, including 35,850 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 0.68 (35850 hom., cov: 31)
• Consequence: ABAT NM_020686.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.660
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABAT	NM_020686.6	c.-42+12454G>C		intron_variant	Intron 1 of 15	ENST00000268251.13	NP_065737.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABAT	ENST00000268251.13	c.-42+12454G>C		intron_variant	Intron 1 of 15	1	NM_020686.6	ENSP00000268251.8
ABAT	ENST00000564714.5	c.-64+12454G>C		intron_variant	Intron 1 of 5	3		ENSP00000456392.1
ABAT	ENST00000563992.1	n.95+12454G>C		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.685 AC: 103994 AN: 151852 Hom.: 35821 Cov.: 31

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.824

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.691

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.685 AC: 104071 AN: 151970 Hom.: 35850 Cov.: 31 AF XY: 0.683 AC XY: 50754 AN XY: 74266

African (AFR) AF: 0.650 AC: 26947 AN: 41448

American (AMR) AF: 0.656 AC: 10029 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.711 AC: 2467 AN: 3468

East Asian (EAS) AF: 0.824 AC: 4237 AN: 5144

South Asian (SAS) AF: 0.733 AC: 3531 AN: 4816

European-Finnish (FIN) AF: 0.648 AC: 6841 AN: 10552

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.703 AC: 47756 AN: 67948

Other (OTH) AF: 0.690 AC: 1458 AN: 2112

Alfa AF: 0.690 Hom.: 4487

Bravo AF: 0.684

Asia WGS AF: 0.756 AC: 2629 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.47
DANN	Benign	0.44
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

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: rs1273350; hg19: chr16-8781022;