16-8768905-C-T

Position:

chr16-8768905-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_020686.6(ABAT):c.748C>T(p.Arg250Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000991 in 1,614,154 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00014 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000094 ( 0 hom. )

Consequence

ABAT
NM_020686.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.32

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 -8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.020848006).

BP6

Variant 16-8768905-C-T is Benign according to our data. Variant chr16-8768905-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 460329.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000144 (22/152272) while in subpopulation EAS AF= 0.0029 (15/5174). AF 95% confidence interval is 0.00179. There are 1 homozygotes in gnomad4. There are 12 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABAT	NM_020686.6 linkuse as main transcript	c.748C>T	p.Arg250Trp	missense_variant	11/16	ENST00000268251.13	NP_065737.2	P80404X5D8S1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABAT	ENST00000268251.13 linkuse as main transcript	c.748C>T	p.Arg250Trp	missense_variant	11/16	1	NM_020686.6	ENSP00000268251.8		P80404

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00289

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000223

AC:

AN:

251482

Hom.:

AF XY:

0.000243

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00272

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000944

AC:

138

AN:

1461882

Hom.:

Cov.:

AF XY:

0.0000990

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00227

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000225

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000144

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00290

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000125

ExAC

AF:

0.000222

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Gamma-aminobutyric acid transaminase deficiency

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 12, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.66

D;D;.;D;D

Eigen

Benign

-0.098

Eigen_PC

Benign

0.0040

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.96

.;D;D;.;D

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.021

T;T;T;T;T

MetaSVM

Uncertain

-0.19

MutationAssessor

Uncertain

2.6

M;M;.;M;.

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-4.7

D;D;D;D;D

REVEL

Uncertain

0.47

Sift

Uncertain

0.021

D;D;D;D;D

Sift4G

Uncertain

0.0070

D;D;D;D;D

Polyphen

0.092

B;B;.;B;.

Vest4

0.50

MutPred

0.45

Gain of ubiquitination at K252 (P = 0.0573);Gain of ubiquitination at K252 (P = 0.0573);.;Gain of ubiquitination at K252 (P = 0.0573);Gain of ubiquitination at K252 (P = 0.0573);

MVP

0.85

MPC

0.32

ClinPred

0.16

GERP RS

3.5

Varity_R

0.48

gMVP

0.87

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