rs150301327
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_014845.6(FIG4):āc.1940A>Gā(p.Tyr647Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000633 in 1,564,846 control chromosomes in the GnomAD database, including 1 homozygotes. 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 (ā ā ).
Frequency
Consequence
NM_014845.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152152Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000876 AC: 22AN: 251084Hom.: 0 AF XY: 0.000125 AC XY: 17AN XY: 135718
GnomAD4 exome AF: 0.0000616 AC: 87AN: 1412576Hom.: 1 Cov.: 23 AF XY: 0.0000737 AC XY: 52AN XY: 705962
GnomAD4 genome AF: 0.0000788 AC: 12AN: 152270Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4AN XY: 74460
ClinVar
Submissions by phenotype
Amyotrophic lateral sclerosis type 11 Uncertain:2
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This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
Charcot-Marie-Tooth disease type 4J Uncertain:2
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This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
not provided Uncertain:2
FIG4: PM2 -
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Charcot-Marie-Tooth disease Uncertain:1
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Inborn genetic diseases Uncertain:1
The c.1940A>G (p.Y647C) alteration is located in exon 17 (coding exon 17) of the FIG4 gene. This alteration results from a A to G substitution at nucleotide position 1940, causing the tyrosine (Y) at amino acid position 647 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Charcot-Marie-Tooth disease type 4 Uncertain:1
This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 647 of the FIG4 protein (p.Tyr647Cys). This variant is present in population databases (rs150301327, gnomAD 0.02%). This missense change has been observed in individual(s) with amyotropic lateral sclerosis and Charcot-Marie-Tooth disease (PMID: 19118816, 25614874, 28051077). ClinVar contains an entry for this variant (Variation ID: 254671). 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: "Benign"; 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. -
not specified Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at