Variant chr1-47416265-TCGGCGGCCCCTGCGGTCCCGGAGCCGCGCGGGCAGGGGCTGCCGCAGCCGATGGCGGGGCGCAGCGACATGGATCCGCCCGCCGCGTTCTCTGGCTTCCCTGCCCTGCCAGCGGTCGCGCCGTCGGGGCCGCCGCCGTCGCCGCTCGCAGGAGCCGAGCCAGGGCGGGAGCCAGAGGAGGCGGCGGCTGGCCGCGGAGAGGCGGCCCCCACGCCCGCGCCCGGCCCGGGGCGGCGGCGG-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The 1-47416265-TCGGCGGCCCCTGCGGTCCCGGAGCCGCGCGGGCAGGGGCTGCCGCAGCCGATGGCGGGGCGCAGCGACATGGATCCGCCCGCCGCGTTCTCTGGCTTCCCTGCCCTGCCAGCGGTCGCGCCGTCGGGGCCGCCGCCGTCGCCGCTCGCAGGAGCCGAGCCAGGGCGGGAGCCAGAGGAGGCGGCGGCTGGCCGCGGAGAGGCGGCCCCCACGCCCGCGCCCGGCCCGGGGCGGCGGCGG-T variant causes a coding sequence, 5 prime UTR change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

FOXE3
NM_012186.3 coding_sequence, 5_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.23

Variant links:

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]

FOXE3 links:

LINC01389 (HGNC:):

LINC01389 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXE3	NM_012186.3 linkuse as main transcript			coding_sequence_variant, 5_prime_UTR_variant	1/1	ENST00000335071.4
LINC01389	NR_126355.1 linkuse as main transcript	n.29-6603_29-6365del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXE3	ENST00000335071.4 linkuse as main transcript			coding_sequence_variant, 5_prime_UTR_variant	1/1		NM_012186.3	P1

Frequencies

GnomAD3 genomes

Cov.:

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

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Congenital primary aphakia;C1862839:Anterior segment dysgenesis

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 21, 2019

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. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. This variant has not been reported in the literature in individuals with FOXE3-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change deletes 202 nucleotides from exon 1 of the FOXE3 mRNA (c.-37_202del), affecting the initiator methionine. While it is expected to result in an absent or disrupted protein product, alternate in-frame methionines downstream could potentially rescue the translation initiation.¬†The next in-frame methionine is located at codon 82. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

No publications associated with this variant yet.