rs780242359
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS2BP5_Strong
This summary comes from the ClinGen Evidence Repository: The p.Ser425Pro variant in FOXG1 is present in one XX and one XY individual in gnomAD v2.1.1 (0.00176%) (not sufficient to meet BS1 criteria). The p.Ser425Pro variant is observed in at least 2 unaffected individuals (GeneDx internal database) (BS2). The p.Ser425Pro variant is found in at least 3 patients with an alternate molecular basis of disease (GeneDx internal database) (BP5_Strong). In summary, the p.Ser425Pro variant in FOXG1 is classified as benign based on the ACMG/AMP criteria (BS2, BP5_strong). LINK:https://erepo.genome.network/evrepo/ui/classification/CA314592/MONDO:0100040/035
Frequency
Consequence
NM_005249.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FOXG1 | NM_005249.5 | c.1273T>C | p.Ser425Pro | missense_variant | 1/1 | ENST00000313071.7 | NP_005240.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FOXG1 | ENST00000313071.7 | c.1273T>C | p.Ser425Pro | missense_variant | 1/1 | 6 | NM_005249.5 | ENSP00000339004.3 | ||
FOXG1 | ENST00000706482.1 | c.1273T>C | p.Ser425Pro | missense_variant | 2/2 | ENSP00000516406.1 | ||||
LINC01551 | ENST00000675861.1 | n.374+2539T>C | intron_variant |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152122Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251334Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135876
GnomAD4 exome AF: 0.0000322 AC: 47AN: 1461870Hom.: 0 Cov.: 34 AF XY: 0.0000303 AC XY: 22AN XY: 727240
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152122Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74290
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 16, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 15, 2020 | - - |
FOXG1 disorder Benign:1
Benign, reviewed by expert panel | curation | ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel | Apr 18, 2024 | The p.Ser425Pro variant in FOXG1 is present in one XX and one XY individual in gnomAD v2.1.1 (0.00176%) (not sufficient to meet BS1 criteria). The p.Ser425Pro variant is observed in at least 2 unaffected individuals (GeneDx internal database) (BS2). The p.Ser425Pro variant is found in at least 3 patients with an alternate molecular basis of disease (GeneDx internal database) (BP5_Strong). In summary, the p.Ser425Pro variant in FOXG1 is classified as benign based on the ACMG/AMP criteria (BS2, BP5_strong). - |
Rett syndrome, congenital variant Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 18, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at