16-8735794-C-T
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_020686.6(ABAT):c.55C>T(p.Arg19Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000678 in 1,605,756 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0032 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00042 ( 5 hom. )
Consequence
ABAT
NM_020686.6 missense
NM_020686.6 missense
Scores
3
15
Clinical Significance
Conservation
PhyloP100: 0.331
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.008483738).
BP6
Variant 16-8735794-C-T is Benign according to our data. Variant chr16-8735794-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 235649.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1, Benign=2}.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00318 (484/152232) while in subpopulation AFR AF= 0.0108 (449/41536). AF 95% confidence interval is 0.00998. There are 3 homozygotes in gnomad4. There are 225 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ABAT | NM_020686.6 | c.55C>T | p.Arg19Cys | missense_variant | 2/16 | ENST00000268251.13 | NP_065737.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ABAT | ENST00000268251.13 | c.55C>T | p.Arg19Cys | missense_variant | 2/16 | 1 | NM_020686.6 | ENSP00000268251.8 |
Frequencies
GnomAD3 genomes AF: 0.00317 AC: 482AN: 152114Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.000935 AC: 220AN: 235212Hom.: 1 AF XY: 0.000668 AC XY: 85AN XY: 127192
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GnomAD4 exome AF: 0.000416 AC: 604AN: 1453524Hom.: 5 Cov.: 31 AF XY: 0.000370 AC XY: 267AN XY: 722210
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GnomAD4 genome AF: 0.00318 AC: 484AN: 152232Hom.: 3 Cov.: 32 AF XY: 0.00302 AC XY: 225AN XY: 74446
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Gamma-aminobutyric acid transaminase deficiency Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 15, 2018 | 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 24, 2024 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | May 19, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2022 | ABAT: BP4, BS1, BS2 - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;.;T;T;.;.;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
.;T;T;T;T;T;T;.;T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
M;.;.;.;M;.;.;M;.
PrimateAI
Benign
T
PROVEAN
Benign
N;N;D;N;N;N;N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T;T;T;T;T;T;D
Sift4G
Uncertain
D;T;D;T;D;D;D;D;D
Polyphen
B;.;.;.;B;.;.;B;.
Vest4
MVP
MPC
0.42
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at