NM_020686.6:c.954+16C>T

Variant names:

• chr16-8772933-C-T
• rs41311266
• NM_020686.6:c.954+16C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_020686.6(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 NM_020686.6 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.88
• Publications: 2 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 -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 Benign/Likely_benign. ClinVar VariationId 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

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.954+16C>T		intron	N/A	NP_065737.2
	ABAT	NM_001386615.1		c.1050+16C>T		intron	N/A	NP_001373544.1
	ABAT	NM_001386616.1		c.954+16C>T		intron	N/A	NP_001373545.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABAT	ENST00000268251.13	TSL:1 MANE Select	c.954+16C>T		intron	N/A	ENSP00000268251.8
	ABAT	ENST00000569156.5	TSL:1	c.954+16C>T		intron	N/A	ENSP00000454963.1
	ABAT	ENST00000566590.5	TSL:1	n.*694+16C>T		intron	N/A	ENSP00000455198.1

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

GnomAD2 exomes AF: 0.00709 AC: 1782 AN: 251372 AF XY: 0.00771

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 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

African (AFR) AF: 0.00152 AC: 51 AN: 33446

American (AMR) AF: 0.00313 AC: 140 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0400 AC: 1046 AN: 26128

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39698

South Asian (SAS) AF: 0.0111 AC: 955 AN: 86198

European-Finnish (FIN) AF: 0.000562 AC: 30 AN: 53392

Middle Eastern (MID) AF: 0.0256 AC: 130 AN: 5078

European-Non Finnish (NFE) AF: 0.00749 AC: 8326 AN: 1111918

Other (OTH) AF: 0.00944 AC: 569 AN: 60286

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

African (AFR) AF: 0.00135 AC: 56 AN: 41482

American (AMR) AF: 0.00439 AC: 67 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0383 AC: 133 AN: 3472

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5168

South Asian (SAS) AF: 0.0102 AC: 49 AN: 4806

European-Finnish (FIN) AF: 0.000662 AC: 7 AN: 10582

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00744 AC: 506 AN: 68016

Other (OTH) AF: 0.0104 AC: 22 AN: 2114

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jul 19, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

May 03, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.083
DANN	Benign	0.66
PhyloP100		-1.9
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		1.8
Mutation Taster		=100/0	polymorphism

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: rs41311266; hg19: chr16-8866790;