chr3-179401317-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_021629.4(GNB4):c.919G>T(p.Val307Phe) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000207 in 1,449,128 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. V307V) has been classified as Likely benign.
Frequency
Consequence
NM_021629.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNB4 | NM_021629.4 | c.919G>T | p.Val307Phe | missense_variant, splice_region_variant | 10/10 | ENST00000232564.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNB4 | ENST00000232564.8 | c.919G>T | p.Val307Phe | missense_variant, splice_region_variant | 10/10 | 1 | NM_021629.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000207 AC: 3AN: 1449128Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1AN XY: 720844
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease dominant intermediate F Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 12, 2022 | This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 307 of the GNB4 protein (p.Val307Phe). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GNB4-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.