chr14-28767782-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 3P and 3B. PM2PP2BP4_ModerateBP6
The NM_005249.5(FOXG1):c.503G>T(p.Gly168Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000187 in 1,603,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G168A) has been classified as Benign.
Frequency
Consequence
NM_005249.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXG1 | NM_005249.5 | c.503G>T | p.Gly168Val | missense_variant | 1/1 | ENST00000313071.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXG1 | ENST00000313071.7 | c.503G>T | p.Gly168Val | missense_variant | 1/1 | NM_005249.5 | P1 | ||
FOXG1 | ENST00000706482.1 | c.503G>T | p.Gly168Val | missense_variant | 2/2 | P1 | |||
LINC01551 | ENST00000675861.1 | n.374+1769G>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151954Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1451572Hom.: 0 Cov.: 35 AF XY: 0.00000277 AC XY: 2AN XY: 721954
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151954Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74220
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 15, 2013 | p.Gly168Val (GGG>GTG): c.503 G>T in exon 1 of the FOXG1 gene (NM_005249.3). The Gly168Val missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The amino acid substitution is conservative as both Glycine and Valine are uncharged, non-polar amino acid residues. Gly168Val alters a position that is not conserved through evolution, and it does not occur within the forkhead binding domain where all previously reported missense mutations in FOXG1 have been identified, to our knowledge. Several in-silico algorithms predict Gly168Val is non-pathogenic, although one model predicts it may be damaging to the structure/function of the protein. Therefore, based on the currently available information, it is unclear whether Gly168Val is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s). - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 24, 2018 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at