Variant 16-8772933-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020686.6(ABAT):c.954+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00752 in 1,612,984 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0058 ( 7 hom., cov: 31)

Exomes 𝑓: 0.0077 ( 78 hom. )

Consequence

ABAT
NM_020686.6 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.88

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 16-8772933-C-T is Benign according to our data. Variant chr16-8772933-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 445320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00576 (876/152122) while in subpopulation SAS AF= 0.0102 (49/4806). AF 95% confidence interval is 0.00792. There are 7 homozygotes in gnomad4. There are 416 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABAT	NM_020686.6 linkuse as main transcript	c.954+16C>T		intron_variant		ENST00000268251.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABAT	ENST00000268251.13 linkuse as main transcript	c.954+16C>T		intron_variant		1	NM_020686.6	P1

Frequencies

GnomAD3 genomes

AF:

0.00575

AC:

874

AN:

152004

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.00439

Gnomad ASJ

AF:

0.0383

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00998

Gnomad FIN

AF:

0.000662

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00742

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00709

AC:

1782

AN:

251372

Hom.:

AF XY:

0.00771

AC XY:

1048

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00301

Gnomad ASJ exome

AF:

0.0393

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0110

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00754

Gnomad OTH exome

AF:

0.00978

GnomAD4 exome

AF:

0.00770

AC:

11251

AN:

1460862

Hom.:

Cov.:

AF XY:

0.00792

AC XY:

5758

AN XY:

726730

show subpopulations

Gnomad4 AFR exome

AF:

0.00152

Gnomad4 AMR exome

AF:

0.00313

Gnomad4 ASJ exome

AF:

0.0400

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0111

Gnomad4 FIN exome

AF:

0.000562

Gnomad4 NFE exome

AF:

0.00749

Gnomad4 OTH exome

AF:

0.00944

GnomAD4 genome

AF:

0.00576

AC:

876

AN:

152122

Hom.:

Cov.:

AF XY:

0.00559

AC XY:

416

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.00439

Gnomad4 ASJ

AF:

0.0383

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0102

Gnomad4 FIN

AF:

0.000662

Gnomad4 NFE

AF:

0.00744

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0109

Hom.:

Bravo

AF:

0.00611

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Gamma-aminobutyric acid transaminase deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 30, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Jul 19, 2021	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

May 03, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.083

DANN

Benign

0.66

RBP_binding_hub_radar

0.67

RBP_regulation_power_radar

1.8

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

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