chr16-8783734-T-A

Variant names:

• chr16-8783734-T-A
• rs9456
• NM_020686.6:c.*2304T>A

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.*2304T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,152 control chromosomes in the GnomAD database, including 1,595 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1595 hom., cov: 33)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: ABAT NM_020686.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.295
• Publications: 15 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]

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 16-8783734-T-A is Benign according to our data. Variant chr16-8783734-T-A is described in ClinVar as Benign. ClinVar VariationId is 321142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020686.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABAT	NM_020686.6	MANE Select	c.*2304T>A		3_prime_UTR	Exon 16 of 16	NP_065737.2
	ABAT	NM_001386615.1		c.*2304T>A		3_prime_UTR	Exon 17 of 17	NP_001373544.1
	ABAT	NM_001386616.1		c.*2318T>A		3_prime_UTR	Exon 16 of 16	NP_001373545.1	H3BNQ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABAT	ENST00000268251.13	TSL:1 MANE Select	c.*2304T>A		3_prime_UTR	Exon 16 of 16	ENSP00000268251.8	P80404
	ABAT	ENST00000396600.6	TSL:5	c.*2304T>A		3_prime_UTR	Exon 16 of 16	ENSP00000379845.2	P80404
	ABAT	ENST00000909342.1		c.*2304T>A		3_prime_UTR	Exon 17 of 17	ENSP00000579401.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21905 AN: 152028 Hom.: 1598 Cov.: 33

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.0890

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.152

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.144 AC: 21898 AN: 152146 Hom.: 1595 Cov.: 33 AF XY: 0.148 AC XY: 10997 AN XY: 74386

African (AFR) AF: 0.127 AC: 5278 AN: 41510

American (AMR) AF: 0.183 AC: 2791 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0890 AC: 309 AN: 3472

East Asian (EAS) AF: 0.216 AC: 1120 AN: 5182

South Asian (SAS) AF: 0.193 AC: 927 AN: 4814

European-Finnish (FIN) AF: 0.159 AC: 1686 AN: 10594

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9256 AN: 67978

Other (OTH) AF: 0.151 AC: 319 AN: 2114

Alfa AF: 0.143 Hom.: 236

Bravo AF: 0.144

Asia WGS AF: 0.180 AC: 628 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Gamma-aminobutyric acid transaminase deficiency (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	1.8
DANN	Benign	0.83
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

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: rs9456; hg19: chr16-8877591;