6-1611782-ACGGCGGCGGCGG-ACGGCGGCGGCGGCGGCGGCGGCGG

Position:

• chr6-1611782-ACGGCGGCGGCGG-ACGGCGGCGGCGGCGGCGGCGGCGG

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001453.3(FOXC1):​c.1350_1361dupCGGCGGCGGCGG​(p.Gly451_Gly454dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 19)
  • Exomes 𝑓: 0.0000039 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FOXC1 NM_001453.3 disruptive_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.613

Genes affected

FOXC1 (HGNC:3800): (forkhead box C1) This gene belongs to the forkhead family of transcription factors which is characterized by a distinct DNA-binding forkhead domain. The specific function of this gene has not yet been determined; however, it has been shown to play a role in the regulation of embryonic and ocular development. Mutations in this gene cause various glaucoma phenotypes including primary congenital glaucoma, autosomal dominant iridogoniodysgenesis anomaly, and Axenfeld-Rieger anomaly. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXC1	NM_001453.3	c.1350_1361dupCGGCGGCGGCGG	p.Gly451_Gly454dup	disruptive_inframe_insertion	1/1	ENST00000645831.2	NP_001444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXC1	ENST00000645831.2	c.1350_1361dupCGGCGGCGGCGG	p.Gly451_Gly454dup	disruptive_inframe_insertion	1/1		NM_001453.3	ENSP00000493906.1

Frequencies

GnomAD3 genomes AF: 0.0000140 AC: 2 AN: 143040 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000682

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000154

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000385 AC: 5 AN: 1297676 Hom.: 0 Cov.: 33 AF XY: 0.00000469 AC XY: 3 AN XY: 639924

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000420

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000144

Gnomad4 FIN exome AF: 0.0000301

Gnomad4 NFE exome AF: 0.00000193

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000140 AC: 2 AN: 143118 Hom.: 0 Cov.: 19 AF XY: 0.0000144 AC XY: 1 AN XY: 69634

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000682

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000154

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Anterior segment dysgenesis 3;C2678503:Axenfeld-Rieger syndrome type 3 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Feb 21, 2024

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs398123612; hg19: chr6-1612017;