6-109789610-A-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_014845.6(FIG4):āc.2113A>Gā(p.Thr705Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000589 in 1,613,120 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 ). Synonymous variant affecting the same amino acid position (i.e. T705T) has been classified as Likely benign.
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.2113A>G | p.Thr705Ala | missense_variant | 19/23 | ENST00000230124.8 | |
FIG4 | XM_011536281.4 | c.2050A>G | p.Thr684Ala | missense_variant | 19/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FIG4 | ENST00000230124.8 | c.2113A>G | p.Thr705Ala | missense_variant | 19/23 | 1 | NM_014845.6 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152248Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251360Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135864
GnomAD4 exome AF: 0.0000630 AC: 92AN: 1460872Hom.: 0 Cov.: 30 AF XY: 0.0000619 AC XY: 45AN XY: 726828
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152248Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74378
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 27, 2021 | The p.T705A variant (also known as c.2113A>G), located in coding exon 19 of the FIG4 gene, results from an A to G substitution at nucleotide position 2113. The threonine at codon 705 is replaced by alanine, an amino acid with similar properties. This amino acid position is not 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 18, 2016 | - - |
FIG4-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 22, 2023 | The FIG4 c.2113A>G variant is predicted to result in the amino acid substitution p.Thr705Ala. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0054% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-110110813-A-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Charcot-Marie-Tooth disease type 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 22, 2022 | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 705 of the FIG4 protein (p.Thr705Ala). This variant is present in population databases (rs766031746, gnomAD 0.006%). 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: 287039). 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