17-76137508-C-G

Variant names:

• chr17-76137508-C-G
• NM_001454.4:c.1111G>C

Variant summary

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

The NM_001454.4(FOXJ1):​c.1111G>C​(p.Asp371His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D371N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FOXJ1 NM_001454.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.15

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]

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=0.32308862).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXJ1	NM_001454.4	c.1111G>C	p.Asp371His	missense_variant	Exon 3 of 3	ENST00000322957.7	NP_001445.2
FOXJ1	XM_047435666.1	c.1111G>C	p.Asp371His	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	c.1111G>C	p.Asp371His	missense_variant	Exon 3 of 3	1	NM_001454.4	ENSP00000323880.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

FOXJ1-related disorder Uncertain:1

Jul 09, 2024

PreventionGenetics, part of Exact Sciences

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

The FOXJ1 c.1111G>C variant is predicted to result in the amino acid substitution p.Asp371His. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.32	T
MetaSVM	Uncertain	0.54	D
MutationAssessor	Benign	1.8	L
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.60
Sift	Benign	0.13	T
Sift4G	Benign	0.43	T
Polyphen		0.62	P
Vest4		0.28
MutPred		0.21		Loss of disorder (P = 0.1456);
MVP		0.94
MPC		1.2
ClinPred		0.88	D
GERP RS		5.2
Varity_R		0.42
gMVP		0.68

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.

Other links and lift over

hg19: chr17-74133589;