rs1064797186
Variant summary
Our verdict is Pathogenic. Variant got 19 ACMG points: 19P and 0B. PM1PM2PM5PP2PP3_StrongPP5_Very_Strong
The NM_005249.5(FOXG1):c.685A>C(p.Ile229Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I229K) has been classified as Likely pathogenic.
Frequency
Consequence
NM_005249.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXG1 | NM_005249.5 | c.685A>C | p.Ile229Leu | missense_variant | 1/1 | ENST00000313071.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXG1 | ENST00000313071.7 | c.685A>C | p.Ile229Leu | missense_variant | 1/1 | NM_005249.5 | P1 | ||
FOXG1 | ENST00000706482.1 | c.685A>C | p.Ile229Leu | missense_variant | 2/2 | P1 | |||
LINC01551 | ENST00000675861.1 | n.374+1951A>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 34
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
FOXG1 disorder Pathogenic:1
Likely pathogenic, reviewed by expert panel | curation | ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel | Feb 18, 2022 | The p.Ile229Leu variant occurs in the well-characterized Forkhead functional domain of the FOXG1 gene (PMID 18571142, 28661489) (PM1). The p.Ile229Leu variant in FOXG1 occurs in the de novo state (biological parentage unconfirmed) in an individual with intellectual disability and seizures (Genetic Services Laboratory, University of Chicago internal data)(PM6). Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance (PP3). The p.Ile229Leu variant in FOXG1 is absent in gnomAD (PM2_supporting). In summary, the p.Ile229Leu variant in FOXG1 is classified as likely pathogenic for FOXG1 disorder based on the ACMG/AMP criteria (PM1, PM6, PP3, PM2_supporting). - |
Rett syndrome, congenital variant Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 09, 2016 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at