chr16-8748103-T-C

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.169-5T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 1,611,106 control chromosomes in the GnomAD database, including 291,683 homozygotes. In-silico tool predicts 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 0.50 ( 21342 hom., cov: 33)

Exomes 𝑓: 0.60 ( 270341 hom. )

Consequence

ABAT
NM_020686.6 splice_region, intron

Scores

Splicing: ADA: 0.0001748

Clinical Significance

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

Conservation

PhyloP100: 1.67

Publications

13 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=-0.44).

BP6

Variant 16-8748103-T-C is Benign according to our data. Variant chr16-8748103-T-C is described in ClinVar as [Benign]. Clinvar id is 320843.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABAT	NM_020686.6 link	c.169-5T>C		splice_region_variant, intron_variant	Intron 3 of 15	ENST00000268251.13	NP_065737.2	P80404X5D8S1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABAT	ENST00000268251.13 link	c.169-5T>C		splice_region_variant, intron_variant	Intron 3 of 15	1	NM_020686.6	ENSP00000268251.8		P80404

Frequencies

GnomAD3 genomes

AF:

0.500

AC:

76046

AN:

151942

Hom.:

21338

Cov.:

show subpopulations

Gnomad AFR

AF:

0.226

Gnomad AMI

AF:

0.520

Gnomad AMR

AF:

0.593

Gnomad ASJ

AF:

0.524

Gnomad EAS

AF:

0.595

Gnomad SAS

AF:

0.534

Gnomad FIN

AF:

0.643

Gnomad MID

AF:

0.434

Gnomad NFE

AF:

0.614

Gnomad OTH

AF:

0.513

GnomAD2 exomes

AF:

0.580

AC:

145769

AN:

251114

AF XY:

0.581

show subpopulations

Gnomad AFR exome

AF:

0.216

Gnomad AMR exome

AF:

0.670

Gnomad ASJ exome

AF:

0.523

Gnomad EAS exome

AF:

0.585

Gnomad FIN exome

AF:

0.647

Gnomad NFE exome

AF:

0.608

Gnomad OTH exome

AF:

0.577

GnomAD4 exome

AF:

0.604

AC:

881294

AN:

1459048

Hom.:

270341

Cov.:

AF XY:

0.602

AC XY:

436902

AN XY:

725988

show subpopulations

African (AFR)

AF:

0.207

AC:

6921

AN:

33434

American (AMR)

AF:

0.665

AC:

29713

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.524

AC:

13678

AN:

26096

East Asian (EAS)

AF:

0.634

AC:

25117

AN:

39602

South Asian (SAS)

AF:

0.544

AC:

46864

AN:

86164

European-Finnish (FIN)

AF:

0.646

AC:

34437

AN:

53332

Middle Eastern (MID)

AF:

0.484

AC:

2785

AN:

5754

European-Non Finnish (NFE)

AF:

0.619

AC:

687069

AN:

1109676

Other (OTH)

AF:

0.576

AC:

34710

AN:

60304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

15581

31162

46742

62323

77904

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18334

36668

55002

73336

91670

<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:

0.500

AC:

76067

AN:

152058

Hom.:

21342

Cov.:

AF XY:

0.502

AC XY:

37332

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.225

AC:

9358

AN:

41512

American (AMR)

AF:

0.593

AC:

9053

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.524

AC:

1820

AN:

3470

East Asian (EAS)

AF:

0.595

AC:

3080

AN:

5180

South Asian (SAS)

AF:

0.534

AC:

2573

AN:

4820

European-Finnish (FIN)

AF:

0.643

AC:

6796

AN:

10572

Middle Eastern (MID)

AF:

0.435

AC:

128

AN:

294

European-Non Finnish (NFE)

AF:

0.614

AC:

41703

AN:

67942

Other (OTH)

AF:

0.515

AC:

1085

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1737

3475

5212

6950

8687

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

670

1340

2010

2680

3350

<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:

0.558

Hom.:

17753

Bravo

AF:

0.487

Asia WGS

AF:

0.562

AC:

1950

AN:

3474

EpiCase

AF:

0.595

EpiControl

AF:

0.594

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

- -

Feb 19, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Apr 20, 2017

Athena Diagnostics

Significance: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: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. -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

7.5

(source)

DANN

Benign

0.70

PhyloP100

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=94/6

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00017

dbscSNV1_RF

Benign

0.012

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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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