17-76140064-T-G

Variant names:

• chr17-76140064-T-G
• rs1286036482
• NM_001454.4:c.332A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001454.4(FOXJ1):​c.332A>C​(p.Asp111Ala) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D111N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FOXJ1 NM_001454.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.06
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2964658).

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.332A>C	p.Asp111Ala	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.332A>C	p.Asp111Ala	missense	Exon 2 of 3	ENSP00000323880.4	Q92949
	FOXJ1	ENST00000861552.1		c.332A>C	p.Asp111Ala	missense	Exon 2 of 3	ENSP00000531611.1
	FOXJ1	ENST00000861553.1		c.332A>C	p.Asp111Ala	missense	Exon 1 of 2	ENSP00000531612.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.39	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.73	T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.30	T
MetaSVM	Uncertain	0.31	D
MutationAssessor	Benign	1.6	L
PhyloP100		5.1
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.49
Sift	Uncertain	0.024	D
Sift4G	Benign	0.080	T
Polyphen		0.86	P
Vest4		0.24
MutPred		0.13		Gain of glycosylation at P109 (P = 0.1167)
MVP		0.70
MPC		1.2
ClinPred		0.91	D
GERP RS		5.0
Varity_R		0.26
gMVP		0.67
Mutation Taster		=54/46	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: rs1286036482; hg19: chr17-74136145;