rs1555383878
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2
The NM_000814.6(GABRB3):c.175C>T(p.Pro59Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000686 in 1,458,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000814.6 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GABRB3 | NM_000814.6 | c.175C>T | p.Pro59Ser | missense_variant, splice_region_variant | 3/9 | ENST00000311550.10 | NP_000805.1 | |
GABRB3 | NM_021912.5 | c.175C>T | p.Pro59Ser | missense_variant, splice_region_variant | 3/9 | NP_068712.1 | ||
GABRB3 | NM_001278631.2 | c.-177C>T | splice_region_variant | 3/10 | NP_001265560.1 | |||
GABRB3 | NM_001278631.2 | c.-177C>T | 5_prime_UTR_variant | 3/10 | NP_001265560.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GABRB3 | ENST00000311550.10 | c.175C>T | p.Pro59Ser | missense_variant, splice_region_variant | 3/9 | 1 | NM_000814.6 | ENSP00000308725.5 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD4 exome AF: 0.00000686 AC: 10AN: 1458070Hom.: 0 Cov.: 31 AF XY: 0.00000965 AC XY: 7AN XY: 725330
GnomAD4 genome Cov.: 34
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 28, 2018 | The p.P59S variant (also known as c.175C>T), located in coding exon 3 of the GABRB3 gene, results from a C to T substitution at nucleotide position 175. The proline at codon 59 is replaced by serine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Epilepsy, childhood absence, susceptibility to, 1;C2677087:Epilepsy, childhood absence, susceptibility to, 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 13, 2020 | This sequence change replaces proline with serine at codon 59 of the GABRB3 protein (p.Pro59Ser). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and serine. In summary, this variant has uncertain impact on GABRB3 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with a GABRB3-related disease. This variant is not present in population databases (ExAC no frequency). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at