chr17-76140064-T-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001454.4(FOXJ1):​c.332A>T​(p.Asp111Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000687 in 1,456,044 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 10 AD gene.

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>T	p.Asp111Val	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>T	p.Asp111Val	missense	Exon 2 of 3	ENSP00000323880.4	Q92949
	FOXJ1	ENST00000861552.1		c.332A>T	p.Asp111Val	missense	Exon 2 of 3	ENSP00000531611.1
	FOXJ1	ENST00000861553.1		c.332A>T	p.Asp111Val	missense	Exon 1 of 2	ENSP00000531612.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000413 AC: 1 AN: 242036 AF XY: 0.00000757

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000905

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000687 AC: 10 AN: 1456044 Hom.: 0 Cov.: 33 AF XY: 0.00000690 AC XY: 5 AN XY: 724582

African (AFR) AF: 0.0000299 AC: 1 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47808

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111902

Other (OTH) AF: 0.0000166 AC: 1 AN: 60346

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.68	D
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	D
M_CAP	Pathogenic	0.51	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Uncertain	0.64	D
MutationAssessor	Benign	1.6	L
PhyloP100		5.1
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.020	D
Polyphen		0.97	D
Vest4		0.37
MutPred		0.15		Loss of disorder (P = 0.1592)
MVP		0.83
MPC		1.3
ClinPred		0.93	D
GERP RS		5.0
Varity_R		0.40
gMVP		0.74
Mutation Taster		=56/44	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;