chrX-152652999-CAA-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_018558.4(GABRQ):c.1618_1619del(p.Lys540GlufsTer7) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,458 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 23)
Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )
Consequence
GABRQ
NM_018558.4 frameshift
NM_018558.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.55
Genes affected
GABRQ (HGNC:14454): (gamma-aminobutyric acid type A receptor subunit theta) The gamma-aminobutyric acid (GABA) A receptor is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. This gene encodes the theta subunit of the GABA A receptor. The gene is mapped to chromosome Xq28 in a cluster of genes including those that encode the alpha 3 and epsilon subunits of the GABA A receptor. [provided by RefSeq, Jul 2017]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GABRQ | NM_018558.4 | c.1618_1619del | p.Lys540GlufsTer7 | frameshift_variant | 9/9 | ENST00000598523.3 | |
MAGEA3-DT | XR_938525.3 | n.157-13207_157-13206del | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GABRQ | ENST00000598523.3 | c.1618_1619del | p.Lys540GlufsTer7 | frameshift_variant | 9/9 | 1 | NM_018558.4 | P1 | |
MAGEA3-DT | ENST00000671457.1 | n.130-13207_130-13206del | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD4 exome AF: 9.11e-7 AC: 1AN: 1097458Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 362824
GnomAD4 exome
AF:
AC:
1
AN:
1097458
Hom.:
AF XY:
AC XY:
0
AN XY:
362824
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jun 27, 2023 | Variant summary: GABRQ c.1618_1619delAA (p.Lys540GlufsX7) results in a premature termination codon, predicted to cause a truncation of the encoded protein, however the molecular mechanism of disease attributed to GABRQ is currently unknown. While this variant is not expected to result in nonsense-mediated decay, it is predicted to disrupt the last 93 amino acids of the protein. The variant was absent in 183198 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1618_1619delAA in individuals affected with GABRQ-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have reported clinical-significance assessments for this variant to ClinVar after 2014. GABRQ is shown to tolerate to LOF variants(pLI=0, gnomAD database), and is not associated with established gene-phenotype relationships in the OMIM database. Other variants in this gene have been reported without strong evidence supporting an association to disease (HGMD, LOVD databases). Since available evidence is limited, this variant was classified as uncertain significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at