16-8781189-TGATGGATGGATGGATG-TGATGGATG

Variant names:

• chr16-8781189-TGATGGATG-T
• rs3217123
• NM_020686.6:c.1382-99_1382-92delGATGGATG

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_020686.6(ABAT):​c.1382-99_1382-92delGATGGATG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000413 in 1,418,744 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00045 (0 hom.)
• Consequence: ABAT NM_020686.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890

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]

TMEM186 (HGNC:24530): (transmembrane protein 186) This gene encodes a potential transmembrane protein. [provided by RefSeq, Dec 2012]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0000663 (10/150768) while in subpopulation AMR AF= 0.000527 (8/15176). AF 95% confidence interval is 0.000262. There are 0 homozygotes in gnomad4. There are 6 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABAT	NM_020686.6	c.1382-99_1382-92delGATGGATG		intron_variant	Intron 15 of 15	ENST00000268251.13	NP_065737.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABAT	ENST00000268251.13	c.1382-119_1382-112delGATGGATG		intron_variant	Intron 15 of 15	1	NM_020686.6	ENSP00000268251.8

Frequencies

GnomAD3 genomes AF: 0.0000664 AC: 10 AN: 150652 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000528

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.000483

GnomAD4 exome AF: 0.000454 AC: 576 AN: 1267976 Hom.: 0 AF XY: 0.000428 AC XY: 274 AN XY: 639994

Gnomad4 AFR exome AF: 0.0000999

Gnomad4 AMR exome AF: 0.000181

Gnomad4 ASJ exome AF: 0.000122

Gnomad4 EAS exome AF: 0.0000261

Gnomad4 SAS exome AF: 0.0000608

Gnomad4 FIN exome AF: 0.000246

Gnomad4 NFE exome AF: 0.000560

Gnomad4 OTH exome AF: 0.000260

GnomAD4 genome AF: 0.0000663 AC: 10 AN: 150768 Hom.: 0 Cov.: 0 AF XY: 0.0000815 AC XY: 6 AN XY: 73592

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000527

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000148

Gnomad4 OTH AF: 0.000478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3217123; hg19: chr16-8875046;