chr6-1611567-G-GGGCGGC
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2
The NM_001453.3(FOXC1):c.1136_1141dupGCGGCG(p.Gly379_Gly380dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000493 in 1,142,760 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001453.3 disruptive_inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FOXC1 | NM_001453.3 | c.1136_1141dupGCGGCG | p.Gly379_Gly380dup | disruptive_inframe_insertion | Exon 1 of 1 | ENST00000645831.2 | NP_001444.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000335 AC: 49AN: 146424Hom.: 0 Cov.: 24
GnomAD3 exomes AF: 0.0000737 AC: 1AN: 13566Hom.: 0 AF XY: 0.000113 AC XY: 1AN XY: 8876
GnomAD4 exome AF: 0.000516 AC: 514AN: 996234Hom.: 0 Cov.: 32 AF XY: 0.000500 AC XY: 238AN XY: 475960
GnomAD4 genome AF: 0.000334 AC: 49AN: 146526Hom.: 0 Cov.: 24 AF XY: 0.000379 AC XY: 27AN XY: 71314
ClinVar
Submissions by phenotype
Axenfeld-Rieger syndrome type 3 Uncertain:1
This variant, c.1136_1141dup, results in the insertion of 2 amino acid(s) of the FOXC1 protein (p.Gly379_Gly380dup), 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 FOXC1-related conditions. 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. -
not provided Benign:1
FOXC1: BP3, BS2 -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at