rs377017892
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_014845.6(FIG4):c.2360G>A(p.Ser787Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000713 in 1,613,792 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 (★★).
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
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152206Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250940Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135664
GnomAD4 exome AF: 0.0000759 AC: 111AN: 1461586Hom.: 0 Cov.: 31 AF XY: 0.0000743 AC XY: 54AN XY: 727072
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152206Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74360
ClinVar
Submissions by phenotype
not provided Uncertain:2
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Identified in the single heterozygous state in two individuals with unspecified Charcot-Marie-Tooth disease (Nicholson et al., 2011); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 21705420) -
Inborn genetic diseases Uncertain:1
The p.S787N variant (also known as c.2360G>A), located in coding exon 20 of the FIG4 gene, results from a G to A substitution at nucleotide position 2360. The serine at codon 787 is replaced by asparagine, an amino acid with highly similar properties. This nucleotide position is not well conserved in available vertebrate species. This amino acid position is well 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. -
Yunis-Varon syndrome;C1970011:Charcot-Marie-Tooth disease type 4J;C2675491:Amyotrophic lateral sclerosis type 11;C4013648:Bilateral parasagittal parieto-occipital polymicrogyria Uncertain:1
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Charcot-Marie-Tooth disease type 4 Uncertain:1
This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 787 of the FIG4 protein (p.Ser787Asn). This variant is present in population databases (rs377017892, gnomAD 0.003%). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 21705420). ClinVar contains an entry for this variant (Variation ID: 585870). 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. 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