17-76137604-C-G

Variant names:

• chr17-76137604-C-G
• NM_001454.4:c.1015G>C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001454.4(FOXJ1):​c.1015G>C​(p.Ala339Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000552 in 1,450,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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. A339T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: FOXJ1 NM_001454.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.189

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1296143).
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXJ1	NM_001454.4	c.1015G>C	p.Ala339Pro	missense_variant	Exon 3 of 3	ENST00000322957.7	NP_001445.2
FOXJ1	XM_047435666.1	c.1015G>C	p.Ala339Pro	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.1015G>C	p.Ala339Pro	missense_variant	Exon 3 of 3	1	NM_001454.4	ENSP00000323880.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000552 AC: 8 AN: 1450470 Hom.: 0 Cov.: 31 AF XY: 0.00000556 AC XY: 4 AN XY: 719920

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000633

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	7.4
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.71	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.13	T
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.20
Sift	Benign	0.28	T
Sift4G	Benign	0.29	T
Polyphen		0.20	B
Vest4		0.051
MutPred		0.31		Gain of catalytic residue at P338 (P = 0.0171);
MVP		0.73
MPC		0.54
ClinPred		0.26	T
GERP RS		4.3
Varity_R		0.10
gMVP		0.48

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: chr17-74133685;