rs765169217

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_012186.3(FOXE3):c.16G>A(p.Asp6Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00154 in 1,367,238 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0080 ( 18 hom., cov: 32)

Exomes 𝑓: 0.00074 ( 17 hom. )

Consequence

FOXE3
NM_012186.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.447

Publications

3 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004626423).

BP6

Variant 1-47416331-G-A is Benign according to our data. Variant chr1-47416331-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 287849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00801 (1211/151158) while in subpopulation AFR AF = 0.0279 (1157/41472). AF 95% confidence interval is 0.0266. There are 18 homozygotes in GnomAd4. There are 588 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 18 AR,AD gene

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.16G>A	p.Asp6Asn	missense	Exon 1 of 1	NP_036318.1	Q13461
	LINC01389	NR_126355.1		n.29-6430C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FOXE3	ENST00000335071.4	TSL:6 MANE Select	c.16G>A	p.Asp6Asn	missense	Exon 1 of 1	ENSP00000334472.2	Q13461
LINC01389	ENST00000828805.1		n.207+17032C>T		intron	N/A
LINC01389	ENST00000828806.1		n.92+900C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00796

AC:

1203

AN:

151050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0278

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00224

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00873

GnomAD2 exomes

AF:

0.000669

AC:

AN:

64260

AF XY:

0.000508

show subpopulations

Gnomad AFR exome

AF:

0.0365

Gnomad AMR exome

AF:

0.00115

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000738

AC:

897

AN:

1216080

Hom.:

Cov.:

AF XY:

0.000624

AC XY:

372

AN XY:

596378

show subpopulations

African (AFR)

AF:

0.0300

AC:

759

AN:

25292

American (AMR)

AF:

0.00137

AC:

AN:

21888

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20118

East Asian (EAS)

AF:

0.00

AC:

AN:

26482

South Asian (SAS)

AF:

0.000125

AC:

AN:

56160

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27042

Middle Eastern (MID)

AF:

0.000585

AC:

AN:

3416

European-Non Finnish (NFE)

AF:

0.0000111

AC:

AN:

986918

Other (OTH)

AF:

0.00180

AC:

AN:

48764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

124

166

207

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00801

AC:

1211

AN:

151158

Hom.:

Cov.:

AF XY:

0.00797

AC XY:

588

AN XY:

73752

show subpopulations

African (AFR)

AF:

0.0279

AC:

1157

AN:

41472

American (AMR)

AF:

0.00224

AC:

AN:

15210

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3432

East Asian (EAS)

AF:

0.00

AC:

AN:

5116

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10530

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67286

Other (OTH)

AF:

0.00864

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

116

175

233

291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00903

ExAC

AF:

0.000243

AC:

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (3)

Cardiovascular phenotype (1)

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.071

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.47

MetaRNN

Benign

0.0046

MetaSVM

Benign

-0.41

MutationAssessor

Benign

0.55

PhyloP100

0.45

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.64

REVEL

Benign

0.17

Sift

Benign

0.053

Sift4G

Pathogenic

0.0

Polyphen

0.96

Vest4

0.16

MVP

0.59

ClinPred

0.019

GERP RS

0.43

PromoterAI

0.14

Neutral

(source)

Varity_R

0.041

gMVP

0.068

Mutation Taster

=99/1

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over