chr6-109789643-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3
The NM_014845.6(FIG4):c.2146C>T(p.Arg716Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,613,138 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. R716H) has been classified as Uncertain significance.
Frequency
Consequence
NM_014845.6 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 |
---|---|---|---|---|---|---|---|
FIG4 | NM_014845.6 | c.2146C>T | p.Arg716Cys | missense_variant | 19/23 | ENST00000230124.8 | |
FIG4 | XM_011536281.4 | c.2083C>T | p.Arg695Cys | missense_variant | 19/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FIG4 | ENST00000230124.8 | c.2146C>T | p.Arg716Cys | missense_variant | 19/23 | 1 | NM_014845.6 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152096Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251388Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135870
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461042Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 726884
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152096Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74298
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Jan 31, 2017 | - - |
Charcot-Marie-Tooth disease type 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 22, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 716 of the FIG4 protein (p.Arg716Cys). This variant is present in population databases (rs139235893, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with FIG4-related conditions. ClinVar contains an entry for this variant (Variation ID: 439727). 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: "Probably 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