chr16-8775017-C-T

Variant names:

• chr16-8775017-C-T
• rs774473099
• NM_020686.6:c.1082C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020686.6(ABAT):​c.1082C>T​(p.Thr361Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T361S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABAT NM_020686.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.81
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABAT	NM_020686.6	c.1082C>T	p.Thr361Ile	missense_variant	Exon 13 of 16	ENST00000268251.13	NP_065737.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABAT	ENST00000268251.13	c.1082C>T	p.Thr361Ile	missense_variant	Exon 13 of 16	1	NM_020686.6	ENSP00000268251.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	10
DANN	Benign	0.97
DEOGEN2	Benign	0.41	T;T;.;T;T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.83
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.80	.;T;T;.;T
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.54	D;D;D;D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	0.21	N;N;.;N;.
PhyloP100		2.8
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.2	N;N;N;N;N
REVEL	Uncertain	0.39
Sift	Benign	0.23	T;T;T;T;T
Sift4G	Benign	0.71	T;T;T;T;T
Polyphen		0.11	B;B;.;B;.
Vest4		0.32
MutPred		0.78		Loss of ubiquitination at K358 (P = 0.044);Loss of ubiquitination at K358 (P = 0.044);.;Loss of ubiquitination at K358 (P = 0.044);Loss of ubiquitination at K358 (P = 0.044);
MVP		0.64
MPC		0.73
ClinPred		0.78	D
GERP RS		3.9
Varity_R		0.18
gMVP		0.88

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

Other links and lift over

dbSNP: rs774473099; hg19: chr16-8868874;