Genetic Variant FOXE3:p.Asp8His (chr1-47416337-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012186.3(FOXE3):c.22G>C(p.Asp8His) 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 benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FOXE3
NM_012186.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.595

Publications

0 publications found

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

LINC01389 links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21116945).

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.22G>C	p.Asp8His	missense	Exon 1 of 1	NP_036318.1	Q13461
	LINC01389	NR_126355.1		n.29-6436C>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FOXE3	ENST00000335071.4	TSL:6 MANE Select	c.22G>C	p.Asp8His	missense	Exon 1 of 1	ENSP00000334472.2	Q13461
LINC01389	ENST00000828805.1		n.207+17026C>G		intron	N/A
LINC01389	ENST00000828806.1		n.92+894C>G		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1227040

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

602818

African (AFR)

AF:

0.00

AC:

AN:

25546

American (AMR)

AF:

0.00

AC:

AN:

22892

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20522

East Asian (EAS)

AF:

0.00

AC:

AN:

26520

South Asian (SAS)

AF:

0.00

AC:

AN:

58576

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27450

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3454

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

992796

Other (OTH)

AF:

0.00

AC:

AN:

49284

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Congenital primary aphakia;C1862839:Anterior segment dysgenesis (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.054

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.072

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.51

M_CAP

Pathogenic

0.93

MetaRNN

Benign

0.21

MetaSVM

Uncertain

-0.24

MutationAssessor

Benign

0.34

PhyloP100

0.59

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.37

REVEL

Benign

0.23

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.027

Polyphen

0.77

Vest4

0.078

MutPred

0.16

Gain of methylation at R4 (P = 0.0969)

MVP

0.72

ClinPred

0.23

GERP RS

0.015

PromoterAI

-0.15

Neutral

(source)

Varity_R

0.10

gMVP

0.23

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over