chr17-76140172-A-G

Position:

• chr17-76140172-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001454.4(FOXJ1):​c.224T>C​(p.Leu75Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000762 in 1,313,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: FOXJ1 NM_001454.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.50

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]

RNF157-AS1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2648212).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXJ1	NM_001454.4	c.224T>C	p.Leu75Pro	missense_variant	2/3	ENST00000322957.7	NP_001445.2
FOXJ1	XM_047435666.1	c.224T>C	p.Leu75Pro	missense_variant	1/2		XP_047291622.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXJ1	ENST00000322957.7	c.224T>C	p.Leu75Pro	missense_variant	2/3	1	NM_001454.4	ENSP00000323880.4
RNF157-AS1	ENST00000662723.1	n.89+1652A>G		intron_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.62e-7 AC: 1 AN: 1313194 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 644582

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000501

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.: 32

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2024

The c.224T>C (p.L75P) alteration is located in exon 2 (coding exon 1) of the FOXJ1 gene. This alteration results from a T to C substitution at nucleotide position 224, causing the leucine (L) at amino acid position 75 to be replaced by a proline (P). 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	0.18
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.082
Eigen_PC	Benign	0.085
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.81	T
M_CAP	Pathogenic	0.46	D
MetaRNN	Benign	0.26	T
MetaSVM	Uncertain	0.20	D
MutationAssessor	Benign	0.64	N
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.42	N
REVEL	Uncertain	0.51
Sift	Benign	0.14	T
Sift4G	Benign	0.30	T
Polyphen		0.29	B
Vest4		0.31
MutPred		0.32		Gain of relative solvent accessibility (P = 0.005);
MVP		0.81
MPC		1.4
ClinPred		0.65	D
GERP RS		5.0
Varity_R		0.32
gMVP		0.74

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

Other links and lift over

dbSNP: rs1364290580; hg19: chr17-74136253;