rs1731017

Variant names:

• chr16-8746097-A-G
• rs1731017
• NM_020686.6:c.167A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-8746097-A-G
• chr16-8746097-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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. 17/23 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
• Publications: 36 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 320841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABAT	NM_020686.6	c.167A>G	p.Gln56Arg	missense_variant, splice_region_variant	Exon 3 of 16	ENST00000268251.13	NP_065737.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABAT	ENST00000268251.13	c.167A>G	p.Gln56Arg	missense_variant, splice_region_variant	Exon 3 of 16	1	NM_020686.6	ENSP00000268251.8

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81051 AN: 151816 Hom.: 22937 Cov.: 31

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

GnomAD2 exomes AF: 0.591 AC: 148349 AN: 250938 AF XY: 0.589

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 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.: 35 AF XY: 0.608 AC XY: 441590 AN XY: 725956

African (AFR) AF: 0.319 AC: 10653 AN: 33426

American (AMR) AF: 0.673 AC: 30066 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 14094 AN: 26124

East Asian (EAS) AF: 0.634 AC: 25156 AN: 39674

South Asian (SAS) AF: 0.545 AC: 46990 AN: 86172

European-Finnish (FIN) AF: 0.647 AC: 34536 AN: 53358

Middle Eastern (MID) AF: 0.493 AC: 2532 AN: 5140

European-Non Finnish (NFE) AF: 0.623 AC: 692064 AN: 1110346

Other (OTH) AF: 0.587 AC: 35357 AN: 60260

GnomAD4 genome AF: 0.534 AC: 81089 AN: 151936 Hom.: 22948 Cov.: 31 AF XY: 0.534 AC XY: 39649 AN XY: 74250

African (AFR) AF: 0.331 AC: 13709 AN: 41416

American (AMR) AF: 0.610 AC: 9313 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1871 AN: 3464

East Asian (EAS) AF: 0.594 AC: 3063 AN: 5156

South Asian (SAS) AF: 0.535 AC: 2576 AN: 4812

European-Finnish (FIN) AF: 0.644 AC: 6801 AN: 10554

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.618 AC: 41999 AN: 67958

Other (OTH) AF: 0.545 AC: 1151 AN: 2112

Alfa AF: 0.591 Hom.: 134899

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

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

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	T
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	N
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	T
MutationAssessor	Benign	-0.90	N;.;.;N;.;.;N;.
PhyloP100		0.51
PrimateAI	Benign	0.28	T
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	T
GERP RS		-2.9
Varity_R		0.033
gMVP		0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1731017; hg19: chr16-8839954; COSMIC: COSV51628639; COSMIC: COSV51628639;