rs1731017

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020686.6(ABAT):c.167A>G(p.Gln56Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 1,611,140 control chromosomes in the GnomAD database, including 297,905 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 22948 hom., cov: 31)

Exomes 𝑓: 0.61 ( 274957 hom. )

Consequence

ABAT
NM_020686.6 missense, splice_region

Scores

Splicing: ADA: 0.01633

Clinical Significance

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

Conservation

PhyloP100: 0.508

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.218295E-6).

BP6

Variant 16-8746097-A-G is Benign according to our data. Variant chr16-8746097-A-G is described in ClinVar as [Benign]. Clinvar id is 320841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-8746097-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABAT	NM_020686.6 link	c.167A>G	p.Gln56Arg	missense_variant, splice_region_variant	Exon 3 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.167A>G	p.Gln56Arg	missense_variant, splice_region_variant	Exon 3 of 16	1	NM_020686.6	ENSP00000268251.8		P80404

Frequencies

GnomAD3 genomes

AF:

0.534

AC:

81051

AN:

151816

Hom.:

22937

Cov.:

show subpopulations

Gnomad AFR

AF:

0.331

Gnomad AMI

AF:

0.522

Gnomad AMR

AF:

0.610

Gnomad ASJ

AF:

0.540

Gnomad EAS

AF:

0.595

Gnomad SAS

AF:

0.536

Gnomad FIN

AF:

0.644

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.618

Gnomad OTH

AF:

0.543

GnomAD3 exomes

AF:

0.591

AC:

148349

AN:

250938

Hom.:

44836

AF XY:

0.589

AC XY:

79920

AN XY:

135596

show subpopulations

Gnomad AFR exome

AF:

0.321

Gnomad AMR exome

AF:

0.677

Gnomad ASJ exome

AF:

0.538

Gnomad EAS exome

AF:

0.584

Gnomad SAS exome

AF:

0.541

Gnomad FIN exome

AF:

0.649

Gnomad NFE exome

AF:

0.612

Gnomad OTH exome

AF:

0.585

GnomAD4 exome

AF:

0.611

AC:

891448

AN:

1459204

Hom.:

274957

Cov.:

AF XY:

0.608

AC XY:

441590

AN XY:

725956

show subpopulations

Gnomad4 AFR exome

AF:

0.319

Gnomad4 AMR exome

AF:

0.673

Gnomad4 ASJ exome

AF:

0.540

Gnomad4 EAS exome

AF:

0.634

Gnomad4 SAS exome

AF:

0.545

Gnomad4 FIN exome

AF:

0.647

Gnomad4 NFE exome

AF:

0.623

Gnomad4 OTH exome

AF:

0.587

GnomAD4 genome

AF:

0.534

AC:

81089

AN:

151936

Hom.:

22948

Cov.:

AF XY:

0.534

AC XY:

39649

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.331

Gnomad4 AMR

AF:

0.610

Gnomad4 ASJ

AF:

0.540

Gnomad4 EAS

AF:

0.594

Gnomad4 SAS

AF:

0.535

Gnomad4 FIN

AF:

0.644

Gnomad4 NFE

AF:

0.618

Gnomad4 OTH

AF:

0.545

Alfa

AF:

0.597

Hom.:

70309

Bravo

AF:

0.526

TwinsUK

AF:

0.609

AC:

2259

ALSPAC

AF:

0.624

AC:

2405

ESP6500AA

AF:

0.341

AC:

1497

ESP6500EA

AF:

0.603

AC:

5182

ExAC

AF:

0.582

AC:

70716

Asia WGS

AF:

0.570

AC:

1983

AN:

3478

EpiCase

AF:

0.599

EpiControl

AF:

0.598

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 19, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

- -

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 12, 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

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

1.3

DANN

Benign

0.51

DEOGEN2

Benign

0.014

T;T;T;T;.;.;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.049

.;T;T;T;T;T;.;T

MetaRNN

Benign

0.0000042

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.90

N;.;.;N;.;.;N;.

PrimateAI

Benign

0.28

PROVEAN

Benign

0.37

N;N;N;N;N;N;N;N

REVEL

Benign

0.20

Sift

Benign

0.55

T;T;T;T;T;T;T;T

Sift4G

Benign

0.47

T;T;T;T;T;T;T;T

Polyphen

0.0

B;.;.;B;.;.;B;.

Vest4

0.028

MPC

0.33

ClinPred

0.00091

GERP RS

-2.9

Varity_R

0.033

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.016

dbscSNV1_RF

Benign

0.27

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over