Genetic Variant FOXJ1:p.Asp111Asn (chr17-76140065-C-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_001454.4(FOXJ1):c.331G>A(p.Asp111Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000566 in 1,607,782 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D111G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00025 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

FOXJ1
NM_001454.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 6.11

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:

RNF157-AS1 (HGNC:44127): (RNF157 antisense RNA 1)

RNF157-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07016826).

BP6

Variant 17-76140065-C-T is Benign according to our data. Variant chr17-76140065-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3055097.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 38 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXJ1	NM_001454.4 link	c.331G>A	p.Asp111Asn	missense_variant	Exon 2 of 3	ENST00000322957.7	NP_001445.2	Q92949A0A024R8P1
FOXJ1	XM_047435666.1 link	c.331G>A	p.Asp111Asn	missense_variant	Exon 1 of 2		XP_047291622.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXJ1	ENST00000322957.7 link	c.331G>A	p.Asp111Asn	missense_variant	Exon 2 of 3	1	NM_001454.4	ENSP00000323880.4		Q92949
RNF157-AS1	ENST00000662723.1 link	n.89+1545C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

151970

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000773

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

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

GnomAD3 exomes

AF:

0.0000953

AC:

AN:

241444

Hom.:

AF XY:

0.0000683

AC XY:

AN XY:

131734

show subpopulations

Gnomad AFR exome

AF:

0.00145

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.0000364

AC:

AN:

1455694

Hom.:

Cov.:

AF XY:

0.0000304

AC XY:

AN XY:

724396

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.000250

AC:

AN:

152088

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.000795

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00000603

Hom.:

Bravo

AF:

0.000215

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000116

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

FOXJ1-related disorder

Benign:1

Mar 16, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.80

M_CAP

Pathogenic

0.35

MetaRNN

Benign

0.070

MetaSVM

Uncertain

0.50

MutationAssessor

Benign

1.6

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.3

REVEL

Uncertain

0.40

Sift

Uncertain

0.020

Sift4G

Uncertain

0.052

Polyphen

0.99

Vest4

0.32

MVP

0.83

MPC

1.0

ClinPred

0.20

GERP RS

5.0

Varity_R

0.17

gMVP

0.48

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