NM_004961.4:c.1177C>T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004961.4(GABRE):c.1177C>T(p.Arg393Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000999 in 1,200,849 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_004961.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GABRE | ENST00000370328.4 | c.1177C>T | p.Arg393Cys | missense_variant | Exon 9 of 9 | 1 | NM_004961.4 | ENSP00000359353.3 | ||
GABRE | ENST00000486255.1 | n.4256C>T | non_coding_transcript_exon_variant | Exon 3 of 3 | 1 | |||||
GABRE | ENST00000483564.5 | n.827C>T | non_coding_transcript_exon_variant | Exon 4 of 4 | 3 | |||||
GABRE | ENST00000495862.1 | n.*8C>T | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000357 AC: 4AN: 111899Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34063
GnomAD4 exome AF: 0.00000735 AC: 8AN: 1088950Hom.: 0 Cov.: 32 AF XY: 0.00000281 AC XY: 1AN XY: 355490
GnomAD4 genome AF: 0.0000357 AC: 4AN: 111899Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34063
ClinVar
Submissions by phenotype
GABRE-related epilepsy Uncertain:1
The maternally inherited hemizygous c.1177C>T (p.Arg393Cys) missense variant identified in the GABRE gene has not been reported in affected individuals in the literature. The variant has 0.00003575 allele frequency in the gnomAD(v3) database (4 out of 111899 heterozygous alleles, no homozygote or hemizygote) suggesting it is not a common benign variant in the populations represented in that database. The variant is located within the predicted neurotransmitter-gated ion-channel transmembrane region [2] and affects a moderately conserved residue. In silico tools provide conflicting predictions about potential pathogenicity of this variant (CADD score = 21.8, REVEL score = 0.322). Due to the lack of compelling evidence for this variant’s pathogenicity and because the disease-gene association is not yet fully established, the maternally inherited hemizygous c.1177C>T (p.Arg393Cys) missense variant identified in the GABRE gene is reported as a Variant of Uncertain Significance in a Gene of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at