chr14-28767822-G-T
Variant summary
Our verdict is Pathogenic. Variant got 23 ACMG points: 23P and 0B. PS1_Very_StrongPM1PM2PP2PP3_ModeratePP5_Very_Strong
The NM_005249.5(FOXG1):c.543G>T(p.Lys181Asn) variant causes a missense change involving the alteration of a non-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 nucleotide change resulting in same amino acid change has been previously reported as Pathogenicin ClinVar. Synonymous variant affecting the same amino acid position (i.e. K181K) has been classified as Likely benign.
Frequency
Consequence
NM_005249.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 23 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXG1 | NM_005249.5 | c.543G>T | p.Lys181Asn | missense_variant | 1/1 | ENST00000313071.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXG1 | ENST00000313071.7 | c.543G>T | p.Lys181Asn | missense_variant | 1/1 | NM_005249.5 | P1 | ||
FOXG1 | ENST00000706482.1 | c.543G>T | p.Lys181Asn | missense_variant | 2/2 | P1 | |||
LINC01551 | ENST00000675861.1 | n.374+1809G>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1AN: 1461368Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1AN XY: 726998
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jul 20, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28832562, 29453417, 26938784) - |
Rett syndrome, congenital variant Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Victorian Clinical Genetics Services, Murdoch Childrens Research Institute | Sep 02, 2015 | This variant is predicted to create a change of a lysine to an asparagine at position 181. The lysine at this position is located in the forkhead transcription factor domain, and is highly conserved. Physiochemical properties suggest a moderate amino acid change. Grantham assessment is deleterious. In-silico software predicts this variant to be disease-causing. This is a novel variant not present in disease or population databases. It was confirmed to be de novo in the proband. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at