16-8748103-T-C

Variant names:

• chr16-8748103-T-C
• rs1641010
• NM_020686.6:c.169-5T>C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

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

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]

ACMG classification

Verdict is Benign. Variant got -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. Variant chr16-8748103-T-C is described in Lovd as [Benign].
• 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	c.169-5T>C		splice_region_variant, intron_variant	Intron 3 of 15	ENST00000268251.13	NP_065737.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.500 AC: 76046 AN: 151942 Hom.: 21338 Cov.: 33

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

GnomAD3 exomes AF: 0.580 AC: 145769 AN: 251114 Hom.: 43862 AF XY: 0.581 AC XY: 78863 AN XY: 135732

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 SAS exome AF: 0.540

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.: 36 AF XY: 0.602 AC XY: 436902 AN XY: 725988

Gnomad4 AFR exome AF: 0.207

Gnomad4 AMR exome AF: 0.665

Gnomad4 ASJ exome AF: 0.524

Gnomad4 EAS exome AF: 0.634

Gnomad4 SAS exome AF: 0.544

Gnomad4 FIN exome AF: 0.646

Gnomad4 NFE exome AF: 0.619

Gnomad4 OTH exome AF: 0.576

GnomAD4 genome AF: 0.500 AC: 76067 AN: 152058 Hom.: 21342 Cov.: 33 AF XY: 0.502 AC XY: 37332 AN XY: 74338

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.593

Gnomad4 ASJ AF: 0.524

Gnomad4 EAS AF: 0.595

Gnomad4 SAS AF: 0.534

Gnomad4 FIN AF: 0.643

Gnomad4 NFE AF: 0.614

Gnomad4 OTH AF: 0.515

Alfa AF: 0.558 Hom.: 15881

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

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 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	7.5
DANN	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs1641010; hg19: chr16-8841960; COSMIC: COSV51620420; COSMIC: COSV51620420;