17-76137604-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001454.4(FOXJ1):c.1015G>A(p.Ala339Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000618 in 1,602,738 control chromosomes in the GnomAD database, including 4 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00017 ( 2 hom., cov: 32)

Exomes 𝑓: 0.000050 ( 2 hom. )

Consequence

FOXJ1
NM_001454.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.189

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007953793).

BP6

Variant 17-76137604-C-T is Benign according to our data. Variant chr17-76137604-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1803205.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.

BS2

High AC in GnomAd4 at 26 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXJ1	NM_001454.4 link	c.1015G>A	p.Ala339Thr	missense_variant	Exon 3 of 3	ENST00000322957.7	NP_001445.2	Q92949A0A024R8P1
FOXJ1	XM_047435666.1 link	c.1015G>A	p.Ala339Thr	missense_variant	Exon 2 of 2		XP_047291622.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXJ1	ENST00000322957.7 link	c.1015G>A	p.Ala339Thr	missense_variant	Exon 3 of 3	1	NM_001454.4	ENSP00000323880.4		Q92949

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000106

AC:

AN:

236200

Hom.:

AF XY:

0.000124

AC XY:

AN XY:

128652

show subpopulations

Gnomad AFR exome

AF:

0.0000672

Gnomad AMR exome

AF:

0.0000896

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00106

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000949

Gnomad OTH exome

AF:

0.000174

GnomAD4 exome

AF:

0.0000503

AC:

AN:

1450470

Hom.:

Cov.:

AF XY:

0.0000514

AC XY:

AN XY:

719920

show subpopulations

Gnomad4 AFR exome

AF:

0.0000601

Gnomad4 AMR exome

AF:

0.000137

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000458

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000192

Gnomad4 NFE exome

AF:

0.00000814

Gnomad4 OTH exome

AF:

0.000619

GnomAD4 genome

AF:

0.000171

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000966

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000480

Hom.:

Bravo

AF:

0.000144

ExAC

AF:

0.000140

AC:

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Ciliary dyskinesia, primary, 43

Benign:2

Mar 10, 2021

Genetics and Molecular Pathology, SA Pathology

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 10, 2022

Johns Hopkins Genomics, Johns Hopkins University

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Uncertain:1

Dec 14, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1015G>A (p.A339T) alteration is located in exon 3 (coding exon 2) of the FOXJ1 gene. This alteration results from a G to A substitution at nucleotide position 1015, causing the alanine (A) at amino acid position 339 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.42

CADD

Benign

9.0

DANN

Uncertain

0.98

DEOGEN2

Benign

0.16

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.58

M_CAP

Uncertain

0.094

MetaRNN

Benign

0.0080

MetaSVM

Benign

-0.50

MutationAssessor

Benign

0.92

PrimateAI

Benign

0.34

PROVEAN

Benign

0.090

REVEL

Benign

0.11

Sift

Benign

0.68

Sift4G

Benign

0.63

Polyphen

0.0090

Vest4

0.019

MVP

0.36

MPC

0.33

ClinPred

0.036

GERP RS

4.3

Varity_R

0.029

gMVP

0.30

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over