rs1641022

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_020686.6(ABAT):c.984C>A(p.Val328Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 1,613,810 control chromosomes in the GnomAD database, including 138,819 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 9839 hom., cov: 32)

Exomes 𝑓: 0.42 ( 128980 hom. )

Consequence

ABAT
NM_020686.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0640

Publications

18 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, 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

ABAT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 16-8774919-C-A is Benign according to our data. Variant chr16-8774919-C-A is described in ClinVar as [Benign]. Clinvar id is 321082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABAT	NM_020686.6 link	c.984C>A	p.Val328Val	synonymous_variant	Exon 13 of 16	ENST00000268251.13	NP_065737.2	P80404X5D8S1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABAT	ENST00000268251.13 link	c.984C>A	p.Val328Val	synonymous_variant	Exon 13 of 16	1	NM_020686.6	ENSP00000268251.8		P80404

Frequencies

GnomAD3 genomes

AF:

0.332

AC:

50391

AN:

151928

Hom.:

9846

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.341

Gnomad AMR

AF:

0.312

Gnomad ASJ

AF:

0.360

Gnomad EAS

AF:

0.398

Gnomad SAS

AF:

0.385

Gnomad FIN

AF:

0.513

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.426

Gnomad OTH

AF:

0.338

GnomAD2 exomes

AF:

0.388

AC:

97623

AN:

251384

AF XY:

0.396

show subpopulations

Gnomad AFR exome

AF:

0.109

Gnomad AMR exome

AF:

0.331

Gnomad ASJ exome

AF:

0.361

Gnomad EAS exome

AF:

0.393

Gnomad FIN exome

AF:

0.496

Gnomad NFE exome

AF:

0.426

Gnomad OTH exome

AF:

0.379

GnomAD4 exome

AF:

0.416

AC:

608489

AN:

1461762

Hom.:

128980

Cov.:

AF XY:

0.416

AC XY:

302806

AN XY:

727162

show subpopulations

African (AFR)

AF:

0.103

AC:

3451

AN:

33478

American (AMR)

AF:

0.327

AC:

14630

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.366

AC:

9556

AN:

26136

East Asian (EAS)

AF:

0.385

AC:

15276

AN:

39700

South Asian (SAS)

AF:

0.393

AC:

33916

AN:

86256

European-Finnish (FIN)

AF:

0.485

AC:

25908

AN:

53386

Middle Eastern (MID)

AF:

0.378

AC:

2170

AN:

5736

European-Non Finnish (NFE)

AF:

0.432

AC:

480238

AN:

1111956

Other (OTH)

AF:

0.387

AC:

23344

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

21187

42374

63562

84749

105936

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.331

AC:

50383

AN:

152048

Hom.:

9839

Cov.:

AF XY:

0.337

AC XY:

25013

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.120

AC:

5001

AN:

41516

American (AMR)

AF:

0.312

AC:

4772

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.360

AC:

1249

AN:

3466

East Asian (EAS)

AF:

0.398

AC:

2052

AN:

5156

South Asian (SAS)

AF:

0.384

AC:

1850

AN:

4816

European-Finnish (FIN)

AF:

0.513

AC:

5417

AN:

10566

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.426

AC:

28926

AN:

67946

Other (OTH)

AF:

0.334

AC:

705

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1569

3139

4708

6278

7847

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.392

Hom.:

21245

Bravo

AF:

0.309

Asia WGS

AF:

0.348

AC:

1209

AN:

3478

EpiCase

AF:

0.427

EpiControl

AF:

0.427

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 20, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 19, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Gamma-aminobutyric acid transaminase deficiency

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

4.9

(source)

DANN

Benign

0.69

PhyloP100

0.064

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Mutation Taster

=91/9

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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rs1641022

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over