6-109735242-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_014845.6(FIG4):c.590G>T(p.Arg197Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign 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. R197C) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FIG4 | NM_014845.6 | c.590G>T | p.Arg197Leu | missense_variant | 6/23 | ENST00000230124.8 | |
FIG4 | XM_011536281.4 | c.527G>T | p.Arg176Leu | missense_variant | 6/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FIG4 | ENST00000230124.8 | c.590G>T | p.Arg197Leu | missense_variant | 6/23 | 1 | NM_014845.6 | P4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 250992Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135634
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461262Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726944
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease type 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2022 | ClinVar contains an entry for this variant (Variation ID: 566471). This variant has not been reported in the literature in individuals affected with FIG4-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 197 of the FIG4 protein (p.Arg197Leu). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at