3-179405258-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3
The NM_021629.4(GNB4):c.848G>A(p.Arg283His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,614,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R283C) has been classified as Uncertain significance.
Frequency
Consequence
NM_021629.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNB4 | NM_021629.4 | c.848G>A | p.Arg283His | missense_variant | 9/10 | ENST00000232564.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNB4 | ENST00000232564.8 | c.848G>A | p.Arg283His | missense_variant | 9/10 | 1 | NM_021629.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152176Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251416Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135878
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461850Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727228
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152294Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74462
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease dominant intermediate F Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 19, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GNB4 protein function. This variant has not been reported in the literature in individuals affected with GNB4-related conditions. This variant is present in population databases (rs186593898, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 283 of the GNB4 protein (p.Arg283His). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at