Genetic Variant FOXJ1:p.Gly18Arg (chr17-76140344-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001454.4(FOXJ1):c.52G>A(p.Gly18Arg) 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. 13/21 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

FOXJ1
NM_001454.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0790

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.115041494).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXJ1	NM_001454.4 link	c.52G>A	p.Gly18Arg	missense_variant	Exon 2 of 3	ENST00000322957.7	NP_001445.2	Q92949A0A024R8P1
FOXJ1	XM_047435666.1 link	c.52G>A	p.Gly18Arg	missense_variant	Exon 1 of 2		XP_047291622.1
RNF157-AS1	NR_040017.1 link	n.-212C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FOXJ1	ENST00000322957.7 link	c.52G>A	p.Gly18Arg	missense_variant	Exon 2 of 3	1	NM_001454.4	ENSP00000323880.4	Q92949
RNF157-AS1	ENST00000662723.1 link	n.89+1824C>T		intron_variant	Intron 1 of 1
RNF157-AS1	ENST00000585542.1 link	n.-237C>T		upstream_gene_variant		3
RNF157-AS1	ENST00000590137.1 link	n.-212C>T		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1345324

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

663630

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Oct 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FOXJ1: PM2, PS2:Supporting -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Uncertain

0.063

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.62

M_CAP

Benign

0.080

MetaRNN

Benign

0.12

MetaSVM

Uncertain

0.037

MutationAssessor

Benign

0.69

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.62

REVEL

Benign

0.28

Sift

Uncertain

0.014

Sift4G

Uncertain

0.041

Polyphen

0.0040

Vest4

0.14

MutPred

0.15

Loss of catalytic residue at G18 (P = 0.0595);

MVP

0.64

MPC

0.45

ClinPred

0.27

GERP RS

3.6

Varity_R

0.10

gMVP

0.34

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over