rs1175471807
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_005249.5(FOXG1):βc.463_465delβ(p.Glu155del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.0000196 in 1,533,570 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ). Synonymous variant affecting the same amino acid position (i.e. G153G) has been classified as Likely benign.
Frequency
Genomes: π 0.000066 ( 0 hom., cov: 32)
Exomes π: 0.000014 ( 0 hom. )
Consequence
FOXG1
NM_005249.5 inframe_deletion
NM_005249.5 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.04
Genes affected
FOXG1 (HGNC:3811): (forkhead box G1) This locus encodes a member of the fork-head transcription factor family. The encoded protein, which functions as a transcriptional repressor, is highly expressed in neural tissues during brain development. Mutations at this locus have been associated with Rett syndrome and a diverse spectrum of neurodevelopmental disorders defined as part of the FOXG1 syndrome. This gene is disregulated in many types of cancer and is the target of multiple microRNAs that regulate the proliferation of tumor cells. [provided by RefSeq, Jul 2020]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
?
High AC in GnomAd4 at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXG1 | NM_005249.5 | c.463_465del | p.Glu155del | inframe_deletion | 1/1 | ENST00000313071.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXG1 | ENST00000313071.7 | c.463_465del | p.Glu155del | inframe_deletion | 1/1 | NM_005249.5 | P1 | ||
FOXG1 | ENST00000706482.1 | c.463_465del | p.Glu155del | inframe_deletion | 2/2 | P1 | |||
LINC01551 | ENST00000675861.1 | n.374+1729_374+1731del | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000660 AC: 10AN: 151478Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000361 AC: 5AN: 138362Hom.: 0 AF XY: 0.0000528 AC XY: 4AN XY: 75812
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GnomAD4 exome AF: 0.0000145 AC: 20AN: 1382092Hom.: 0 AF XY: 0.0000161 AC XY: 11AN XY: 681422
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GnomAD4 genome ? AF: 0.0000660 AC: 10AN: 151478Hom.: 0 Cov.: 32 AF XY: 0.0000541 AC XY: 4AN XY: 73964
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Rett syndrome, congenital variant Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Human Genetics, Inc, Center for Human Genetics, Inc | Nov 01, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2023 | This variant, c.463_465del, results in the deletion of 1 amino acid(s) of the FOXG1 protein (p.Glu155del), but otherwise preserves the integrity of the reading frame. 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. ClinVar contains an entry for this variant (Variation ID: 547389). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 28, 2018 | The c.463_465delGAG variant (also known as p.E155del) is located in coding exon 1 of the FOXG1 gene. This variant results from an in-frame GAG deletion at nucleotide positions 463 to 465. This results in the in-frame deletion of a glutamic acid at codon 155. This nucleotide position is not well conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at