chr1-47416265-TCGGCGGCCCCTGCGGTCCCGGAGCCGCGCGGGCAGGGGCTGCCGCAGCCGATGGCGGGGCGCAGCGACATGGATCCGCCCGCCGCGTTCTCTGGCTTCCCTGCCCTGCCAGCGGTCGCGCCGTCGGGGCCGCCGCCGTCGCCGCTCGCAGGAGCCGAGCCAGGGCGGGAGCCAGAGGAGGCGGCGGCTGGCCGCGGAGAGGCGGCCCCCACGCCCGCGCCCGGCCCGGGGCGGCGGCGG-T

Variant names:

• chr1-47416265-TCGGCGGCCCCTGCGGTCCCGGAGCCGCGCGGGCAGGGGCTGCCGCAGCCGATGGCGGGGCGCAGCGACATGGATCCGCCCGCCGCGTTCTCTGGCTTCCCTGCCCTGCCAGCGGTCGCGCCGTCGGGGCCGCCGCCGTCGCCGCTCGCAGGAGCCGAGCCAGGGCGGGAGCCAGAGGAGGCGGCGGCTGGCCGCGGAGAGGCGGCCCCCACGCCCGCGCCCGGCCCGGGGCGGCGGCGG-T
• rs2124040836
• NM_012186.3:c.-37_202del

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_012186.3(FOXE3):​c.-37_202del variant causes a 5 prime UTR truncation, exon loss change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FOXE3 NM_012186.3 5_prime_UTR_truncation, exon_loss
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.23
• Publications: 0 publications found

Genes affected

FOXE3 (HGNC:3808): (forkhead box E3) This intronless gene belongs to the forkhead family of transcription factors, which is characterized by a distinct forkhead domain. The protein encoded functions as a lens-specific transcription factor and plays an important role in vertebrate lens formation. Mutations in this gene are associated with anterior segment mesenchymal dysgenesis and congenital primary aphakia. [provided by RefSeq, Dec 2009]

LINC01389 (HGNC:50661): (long intergenic non-protein coding RNA 1389)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012186.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXE3	NM_012186.3	MANE Select	c.-37_202del	p.Met1fs	frameshift start_lost	Exon 1 of 1	NP_036318.1	Q13461
	FOXE3	NM_012186.3	MANE Select	c.-37_202del		5_prime_UTR_truncation exon_loss	Exon 1 of 1	NP_036318.1	Q13461
	LINC01389	NR_126355.1		n.29-6603_29-6365del		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXE3	ENST00000335071.4	TSL:6 MANE Select	c.-50_189del	p.Met1fs	frameshift start_lost	Exon 1 of 1	ENSP00000334472.2	Q13461
	FOXE3	ENST00000335071.4	TSL:6 MANE Select	c.-50_189del		5_prime_UTR_truncation exon_loss	Exon 1 of 1	ENSP00000334472.2	Q13461
	LINC01389	ENST00000828805.1		n.207+16859_207+17097del		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Congenital primary aphakia;C1862839:Anterior segment dysgenesis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.2

Splicing

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

Other links and lift over

dbSNP: rs2124040836; hg19: chr1-47881937;