Genetic Variant FOXJ1:p.Leu421Phe (chr17-76137356-C-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001454.4(FOXJ1):c.1263G>T(p.Leu421Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000212 in 1,484,272 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0012 ( 2 hom., cov: 33)

Exomes 𝑓: 0.000094 ( 2 hom. )

Consequence

FOXJ1
NM_001454.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.488

Publications

0 publications found

Variant links:

Genes affected

FOXJ1 (HGNC:3816): (forkhead box J1) This gene encodes a member of the forkhead family of transcription factors. Similar genes in zebrafish and mouse have been shown to regulate the transcription of genes that control the production of motile cilia. The mouse ortholog also functions in the determination of left-right asymmetry. Polymorphisms in this gene are associated with systemic lupus erythematosus and allergic rhinitis.[provided by RefSeq, Sep 2009]

FOXJ1 Gene-Disease associations (from GenCC):

ciliary dyskinesia, primary, 43
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

FOXJ1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0080010295).

BP6

Variant 17-76137356-C-A is Benign according to our data. Variant chr17-76137356-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3053190.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 189 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001454.4. 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
	FOXJ1	NM_001454.4	MANE Select	c.1263G>T	p.Leu421Phe	missense	Exon 3 of 3	NP_001445.2	Q92949

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FOXJ1	ENST00000322957.7	TSL:1 MANE Select	c.1263G>T	p.Leu421Phe	missense	Exon 3 of 3	ENSP00000323880.4	Q92949
FOXJ1	ENST00000861552.1		c.1263G>T	p.Leu421Phe	missense	Exon 3 of 3	ENSP00000531611.1
FOXJ1	ENST00000861553.1		c.1263G>T	p.Leu421Phe	missense	Exon 2 of 2	ENSP00000531612.1

Frequencies

GnomAD3 genomes

AF:

0.00124

AC:

189

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0122

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000706

AC:

AN:

100526

AF XY:

0.000623

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00346

Gnomad ASJ exome

AF:

0.000226

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000963

GnomAD4 exome

AF:

0.0000938

AC:

125

AN:

1332026

Hom.:

Cov.:

AF XY:

0.0000783

AC XY:

AN XY:

651324

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30320

American (AMR)

AF:

0.00387

AC:

117

AN:

30210

Ashkenazi Jewish (ASJ)

AF:

0.0000463

AC:

AN:

21592

East Asian (EAS)

AF:

0.00

AC:

AN:

35220

South Asian (SAS)

AF:

0.00

AC:

AN:

71336

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4046

European-Non Finnish (NFE)

AF:

0.00000285

AC:

AN:

1051258

Other (OTH)

AF:

0.0000722

AC:

AN:

55424

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00124

AC:

189

AN:

152246

Hom.:

Cov.:

AF XY:

0.00183

AC XY:

136

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41546

American (AMR)

AF:

0.0122

AC:

186

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00103

ExAC

AF:

0.0000513

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

FOXJ1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

Eigen

Benign

0.14

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.76

MetaRNN

Benign

0.0080

MetaSVM

Uncertain

0.63

MutationAssessor

Benign

0.81

PhyloP100

0.49

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.47

Sift

Uncertain

0.015

Sift4G

Uncertain

0.037

Polyphen

0.96

Vest4

0.40

MutPred

0.37

Gain of catalytic residue at L421 (P = 0.0516)

MVP

0.77

MPC

0.98

ClinPred

0.090

GERP RS

4.2

Varity_R

0.13

gMVP

0.37

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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