rs140331779
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_014845.6(FIG4):āc.328A>Gā(p.Ile110Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,611,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_014845.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FIG4 | NM_014845.6 | c.328A>G | p.Ile110Val | missense_variant | 4/23 | ENST00000230124.8 | |
FIG4 | XM_011536281.4 | c.265A>G | p.Ile89Val | missense_variant | 4/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FIG4 | ENST00000230124.8 | c.328A>G | p.Ile110Val | missense_variant | 4/23 | 1 | NM_014845.6 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000151 AC: 23AN: 152186Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251276Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135788
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1459622Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5AN XY: 726336
GnomAD4 genome ? AF: 0.000151 AC: 23AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74366
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 29, 2016 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 20, 2021 | The p.I110V variant (also known as c.328A>G), located in coding exon 4 of the FIG4 gene, results from an A to G substitution at nucleotide position 328. The isoleucine at codon 110 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Charcot-Marie-Tooth disease type 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2021 | This sequence change replaces isoleucine with valine at codon 110 of the FIG4 protein (p.Ile110Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs140331779, ExAC 0.06%). 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: 240927). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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