17-76140107-A-C

Variant names:

• chr17-76140107-A-C
• rs753539463
• NM_001454.4:c.289T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001454.4(FOXJ1):​c.289T>G​(p.Ser97Ala) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S97T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FOXJ1 NM_001454.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.73
• Publications: 0 publications found

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:44127): (RNF157 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14075401).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001454.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXJ1	NM_001454.4	MANE Select	c.289T>G	p.Ser97Ala	missense	Exon 2 of 3	NP_001445.2	Q92949

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXJ1	ENST00000322957.7	TSL:1 MANE Select	c.289T>G	p.Ser97Ala	missense	Exon 2 of 3	ENSP00000323880.4	Q92949
	FOXJ1	ENST00000861552.1		c.289T>G	p.Ser97Ala	missense	Exon 2 of 3	ENSP00000531611.1
	FOXJ1	ENST00000861553.1		c.289T>G	p.Ser97Ala	missense	Exon 1 of 2	ENSP00000531612.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.32	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.34	T
MutationAssessor	Benign	1.4	L
PhyloP100		3.7
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.23
Sift	Benign	0.25	T
Sift4G	Benign	0.36	T
Polyphen		0.033	B
Vest4		0.055
MutPred		0.17		Loss of glycosylation at S97 (P = 0.0121)
MVP		0.73
MPC		0.30
ClinPred		0.40	T
GERP RS		2.7
Varity_R		0.11
gMVP		0.51
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs753539463; hg19: chr17-74136188;