rs796052472
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP5BS2
This summary comes from the ClinGen Evidence Repository: The p.Ser349Ala variant in FOXG1 is present in one XX and three XY individuals in gnomAD v2.1.1 (0.001418%) (not sufficient to meet BS1 criteria). The p.Ser349Ala variant is observed in at least 2 unaffected individuals (GeneDx internal database) (BS2). The p.Ser349Ala variant is found in a patient with an alternate molecular basis of disease (GeneDx internal database) (BP5). In summary, the p.Ser349Ala variant in FOXG1 is classified as likely benign based on the ACMG/AMP criteria (BS2, BP5). LINK:https://erepo.genome.network/evrepo/ui/classification/CA314631/MONDO:0100040/035
Frequency
Consequence
NM_005249.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXG1 | NM_005249.5 | c.1045T>G | p.Ser349Ala | missense_variant | 1/1 | ENST00000313071.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXG1 | ENST00000313071.7 | c.1045T>G | p.Ser349Ala | missense_variant | 1/1 | NM_005249.5 | P1 | ||
FOXG1 | ENST00000706482.1 | c.1045T>G | p.Ser349Ala | missense_variant | 2/2 | P1 | |||
LINC01551 | ENST00000675861.1 | n.374+2311T>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152128Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250796Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135618
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461666Hom.: 0 Cov.: 34 AF XY: 0.00000550 AC XY: 4AN XY: 727166
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152128Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74310
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jan 04, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 26, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 30, 2017 | - - |
Rett syndrome, congenital variant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 15, 2022 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 205497). This variant has not been reported in the literature in individuals affected with FOXG1-related conditions. This variant is present in population databases (rs796052472, gnomAD 0.002%). This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 349 of the FOXG1 protein (p.Ser349Ala). - |
FOXG1 disorder Benign:1
Likely benign, reviewed by expert panel | curation | ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel | Apr 18, 2024 | The p.Ser349Ala variant in FOXG1 is present in one XX and three XY individuals in gnomAD v2.1.1 (0.001418%) (not sufficient to meet BS1 criteria). The p.Ser349Ala variant is observed in at least 2 unaffected individuals (GeneDx internal database) (BS2). The p.Ser349Ala variant is found in a patient with an alternate molecular basis of disease (GeneDx internal database) (BP5). In summary, the p.Ser349Ala variant in FOXG1 is classified as likely benign based on the ACMG/AMP criteria (BS2, BP5). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at