rs149271402

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBS1BS2

The NM_020686.6(ABAT):c.641T>C(p.Met214Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00272 in 1,614,082 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 13 hom. )

Consequence

ABAT
NM_020686.6 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 5.90

Publications

5 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.

PM1

In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 7 uncertain in NM_020686.6

BP4

Computational evidence support a benign effect (MetaRNN=0.018425345).

BP6

Variant 16-8768230-T-C is Benign according to our data. Variant chr16-8768230-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 283525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00219 (333/152268) while in subpopulation NFE AF = 0.00401 (273/68014). AF 95% confidence interval is 0.00362. There are 0 homozygotes in GnomAd4. There are 162 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABAT	NM_020686.6 link	c.641T>C	p.Met214Thr	missense_variant	Exon 10 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.641T>C	p.Met214Thr	missense_variant	Exon 10 of 16	1	NM_020686.6	ENSP00000268251.8		P80404

Frequencies

GnomAD3 genomes

AF:

0.00219

AC:

333

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000721

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00401

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00240

AC:

603

AN:

251488

AF XY:

0.00251

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.00238

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00333

Gnomad NFE exome

AF:

0.00318

Gnomad OTH exome

AF:

0.00342

GnomAD4 exome

AF:

0.00277

AC:

4055

AN:

1461814

Hom.:

Cov.:

AF XY:

0.00282

AC XY:

2051

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.000239

AC:

AN:

33474

American (AMR)

AF:

0.00103

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00245

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00288

AC:

248

AN:

86256

European-Finnish (FIN)

AF:

0.00341

AC:

182

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.00302

AC:

3357

AN:

1112000

Other (OTH)

AF:

0.00248

AC:

150

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

236

473

709

946

1182

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

106

212

318

424

530

<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:

0.00219

AC:

333

AN:

152268

Hom.:

Cov.:

AF XY:

0.00218

AC XY:

162

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

41550

American (AMR)

AF:

0.000720

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00166

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00198

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00401

AC:

273

AN:

68014

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00272

Hom.:

Bravo

AF:

0.00177

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00360

AC:

ExAC

AF:

0.00251

AC:

305

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00251

EpiControl

AF:

0.00184

ClinVar

Significance: Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jun 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ABAT: BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 26, 2018

Athena Diagnostics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Gamma-aminobutyric acid transaminase deficiency

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Sep 28, 2015

Eurofins Ntd Llc (ga)

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ABAT-related disorder

Benign:1

Jan 04, 2021

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.14

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.19

T;T;.;T;T

Eigen

Benign

-0.22

Eigen_PC

Benign

0.050

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.91

.;D;D;.;D

M_CAP

Benign

0.034

MetaRNN

Benign

0.018

T;T;T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Benign

-0.51

N;N;.;N;.

PhyloP100

5.9

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.26

N;N;N;N;N

REVEL

Uncertain

0.35

Sift

Benign

0.29

T;T;T;T;T

Sift4G

Benign

0.35

T;T;T;T;T

Polyphen

0.0

B;B;.;B;.

Vest4

0.67

MVP

0.82

MPC

0.36

ClinPred

0.021

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.26

gMVP

0.78

Mutation Taster

=98/2

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over