14-28767780-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_005249.5(FOXG1):c.501G>T(p.Glu167Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,450,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_005249.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FOXG1 | ENST00000313071.7 | c.501G>T | p.Glu167Asp | missense_variant | Exon 1 of 1 | 6 | NM_005249.5 | ENSP00000339004.3 | ||
FOXG1 | ENST00000706482.1 | c.501G>T | p.Glu167Asp | missense_variant | Exon 2 of 2 | ENSP00000516406.1 | ||||
LINC01551 | ENST00000675861.1 | n.374+1767G>T | intron_variant | Intron 1 of 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000430 AC: 1AN: 232292Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 127416
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1450144Hom.: 0 Cov.: 36 AF XY: 0.00000139 AC XY: 1AN XY: 721086
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Rett syndrome, congenital variant Uncertain:1
This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 167 of the FOXG1 protein (p.Glu167Asp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with FOXG1-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FOXG1 protein function with a negative predictive value of 95%. 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