16-8772933-C-T

Position:

• chr16-8772933-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000268251.13(ABAT):​c.954+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00752 in 1,612,984 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0058 (7 hom., cov: 31)
  • Exomes 𝑓: 0.0077 (78 hom.)
• Consequence: ABAT ENST00000268251.13 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.88

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=-0.88).
• BP6: Variant 16-8772933-C-T is Benign according to our data. Variant chr16-8772933-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 445320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00576 (876/152122) while in subpopulation SAS AF= 0.0102 (49/4806). AF 95% confidence interval is 0.00792. There are 7 homozygotes in gnomad4. There are 416 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABAT	NM_020686.6	c.954+16C>T		intron_variant		ENST00000268251.13	NP_065737.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABAT	ENST00000268251.13	c.954+16C>T		intron_variant		1	NM_020686.6	ENSP00000268251	P1

Frequencies

GnomAD3 genomes AF: 0.00575 AC: 874 AN: 152004 Hom.: 7 Cov.: 31

Gnomad AFR AF: 0.00135

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.00439

Gnomad ASJ AF: 0.0383

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00998

Gnomad FIN AF: 0.000662

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00742

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.00709 AC: 1782 AN: 251372 Hom.: 15 AF XY: 0.00771 AC XY: 1048 AN XY: 135868

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.00301

Gnomad ASJ exome AF: 0.0393

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.0110

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.00754

Gnomad OTH exome AF: 0.00978

GnomAD4 exome AF: 0.00770 AC: 11251 AN: 1460862 Hom.: 78 Cov.: 32 AF XY: 0.00792 AC XY: 5758 AN XY: 726730

Gnomad4 AFR exome AF: 0.00152

Gnomad4 AMR exome AF: 0.00313

Gnomad4 ASJ exome AF: 0.0400

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0111

Gnomad4 FIN exome AF: 0.000562

Gnomad4 NFE exome AF: 0.00749

Gnomad4 OTH exome AF: 0.00944

GnomAD4 genome AF: 0.00576 AC: 876 AN: 152122 Hom.: 7 Cov.: 31 AF XY: 0.00559 AC XY: 416 AN XY: 74366

Gnomad4 AFR AF: 0.00135

Gnomad4 AMR AF: 0.00439

Gnomad4 ASJ AF: 0.0383

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0102

Gnomad4 FIN AF: 0.000662

Gnomad4 NFE AF: 0.00744

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.0109 Hom.: 3

Bravo AF: 0.00611

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Gamma-aminobutyric acid transaminase deficiency Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Jul 19, 2021	- -

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	May 03, 2017	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.083
DANN	Benign	0.66
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		1.8

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: rs41311266; hg19: chr16-8866790;