16-8712564-T-C

Variant names:

• chr16-8712564-T-C
• rs1273385
• NM_020686.6:c.-41-23135T>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.-41-23135T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 151,970 control chromosomes in the GnomAD database, including 37,001 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 0.69 (37001 hom., cov: 31)
• Consequence: ABAT NM_020686.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020686.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABAT	NM_020686.6	MANE Select	c.-41-23135T>C		intron	N/A	NP_065737.2
	ABAT	NM_001386615.1		c.-41-23135T>C		intron	N/A	NP_001373544.1
	ABAT	NM_001386602.1		c.-142-17535T>C		intron	N/A	NP_001373531.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABAT	ENST00000268251.13	TSL:1 MANE Select	c.-41-23135T>C		intron	N/A	ENSP00000268251.8
	ABAT	ENST00000564714.5	TSL:3	c.-63-10203T>C		intron	N/A	ENSP00000456392.1
	ABAT	ENST00000563992.1	TSL:2	n.96-23135T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104538 AN: 151852 Hom.: 36977 Cov.: 31

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.894

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.723

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

GnomAD4 genome AF: 0.688 AC: 104602 AN: 151970 Hom.: 37001 Cov.: 31 AF XY: 0.688 AC XY: 51055 AN XY: 74260

African (AFR) AF: 0.521 AC: 21567 AN: 41410

American (AMR) AF: 0.746 AC: 11390 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 2641 AN: 3472

East Asian (EAS) AF: 0.894 AC: 4601 AN: 5148

South Asian (SAS) AF: 0.761 AC: 3674 AN: 4826

European-Finnish (FIN) AF: 0.671 AC: 7080 AN: 10556

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

European-Non Finnish (NFE) AF: 0.752 AC: 51129 AN: 67974

Other (OTH) AF: 0.721 AC: 1526 AN: 2116

Alfa AF: 0.740 Hom.: 53322

Bravo AF: 0.688

Asia WGS AF: 0.809 AC: 2808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.5
DANN	Benign	0.55
PhyloP100		1.7
PromoterAI		0.017	Neutral
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: rs1273385; hg19: chr16-8806421; COSMIC: COSV51628444;