NM_020686.6:c.1381+9T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020686.6(ABAT):c.1381+9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,608,896 control chromosomes in the GnomAD database, including 73,976 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8679 hom., cov: 32)

Exomes 𝑓: 0.30 ( 65297 hom. )

Consequence

ABAT
NM_020686.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.981

Publications

9 publications found

Variant links:

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 Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet
genetic developmental and epileptic encephalopathy
Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ABAT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 16-8779599-T-C is Benign according to our data. Variant chr16-8779599-T-C is described in ClinVar as Benign. ClinVar VariationId is 321090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.427 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ABAT	NM_020686.6	MANE Select	c.1381+9T>C	intron	N/A	NP_065737.2
ABAT	NM_001386615.1		c.1477+9T>C	intron	N/A	NP_001373544.1
ABAT	NM_001386616.1		c.1381+9T>C	intron	N/A	NP_001373545.1	H3BNQ7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ABAT	ENST00000268251.13	TSL:1 MANE Select	c.1381+9T>C	intron	N/A	ENSP00000268251.8	P80404
ABAT	ENST00000569156.5	TSL:1	c.1381+9T>C	intron	N/A	ENSP00000454963.1	H3BNQ7
ABAT	ENST00000566590.5	TSL:1	n.*1121+9T>C	intron	N/A	ENSP00000455198.1	H3BP84

Frequencies

GnomAD3 genomes

AF:

0.330

AC:

50168

AN:

151830

Hom.:

8664

Cov.:

show subpopulations

Gnomad AFR

AF:

0.432

Gnomad AMI

AF:

0.390

Gnomad AMR

AF:

0.283

Gnomad ASJ

AF:

0.306

Gnomad EAS

AF:

0.364

Gnomad SAS

AF:

0.342

Gnomad FIN

AF:

0.229

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.292

Gnomad OTH

AF:

0.333

GnomAD2 exomes

AF:

0.298

AC:

74451

AN:

249872

AF XY:

0.301

show subpopulations

Gnomad AFR exome

AF:

0.438

Gnomad AMR exome

AF:

0.228

Gnomad ASJ exome

AF:

0.311

Gnomad EAS exome

AF:

0.352

Gnomad FIN exome

AF:

0.231

Gnomad NFE exome

AF:

0.290

Gnomad OTH exome

AF:

0.294

GnomAD4 exome

AF:

0.296

AC:

431751

AN:

1456948

Hom.:

65297

Cov.:

AF XY:

0.299

AC XY:

216492

AN XY:

725150

show subpopulations

African (AFR)

AF:

0.436

AC:

14575

AN:

33392

American (AMR)

AF:

0.234

AC:

10441

AN:

44646

Ashkenazi Jewish (ASJ)

AF:

0.307

AC:

8027

AN:

26120

East Asian (EAS)

AF:

0.349

AC:

13833

AN:

39654

South Asian (SAS)

AF:

0.343

AC:

29544

AN:

86180

European-Finnish (FIN)

AF:

0.232

AC:

12259

AN:

52748

Middle Eastern (MID)

AF:

0.308

AC:

1774

AN:

5760

European-Non Finnish (NFE)

AF:

0.291

AC:

322957

AN:

1108242

Other (OTH)

AF:

0.305

AC:

18341

AN:

60206

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

14846

29692

44538

59384

74230

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10788

21576

32364

43152

53940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.331

AC:

50227

AN:

151948

Hom.:

8679

Cov.:

AF XY:

0.330

AC XY:

24533

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.433

AC:

17916

AN:

41420

American (AMR)

AF:

0.283

AC:

4317

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.306

AC:

1060

AN:

3464

East Asian (EAS)

AF:

0.364

AC:

1881

AN:

5162

South Asian (SAS)

AF:

0.343

AC:

1645

AN:

4802

European-Finnish (FIN)

AF:

0.229

AC:

2423

AN:

10568

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.292

AC:

19836

AN:

67952

Other (OTH)

AF:

0.335

AC:

705

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1682

3365

5047

6730

8412

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

496

992

1488

1984

2480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.306

Hom.:

5742

Bravo

AF:

0.338

Asia WGS

AF:

0.352

AC:

1223

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Gamma-aminobutyric acid transaminase deficiency (3)

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.52

(source)

DANN

Benign

0.59

PhyloP100

-0.98

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over