chr17-76140103-C-G

Variant names:

• chr17-76140103-C-G
• rs761171147
• NM_001454.4:c.293G>C

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.293G>C​(p.Arg98Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000188 in 1,595,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R98Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FOXJ1 NM_001454.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.98
• Publications: 1 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=0.22762164).

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.293G>C	p.Arg98Pro	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.293G>C	p.Arg98Pro	missense	Exon 2 of 3	ENSP00000323880.4	Q92949
	FOXJ1	ENST00000861552.1		c.293G>C	p.Arg98Pro	missense	Exon 2 of 3	ENSP00000531611.1
	FOXJ1	ENST00000861553.1		c.293G>C	p.Arg98Pro	missense	Exon 1 of 2	ENSP00000531612.1

Frequencies

GnomAD3 genomes AF: 0.00000681 AC: 1 AN: 146862 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000252

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000439 AC: 1 AN: 227826 AF XY: 0.00

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: 0.00000972

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1448366 Hom.: 0 Cov.: 33 AF XY: 0.00000139 AC XY: 1 AN XY: 720808

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33396

American (AMR) AF: 0.00 AC: 0 AN: 44328

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26022

East Asian (EAS) AF: 0.00 AC: 0 AN: 39448

South Asian (SAS) AF: 0.00 AC: 0 AN: 85940

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42934

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110456

Other (OTH) AF: 0.00 AC: 0 AN: 60120

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000681 AC: 1 AN: 146862 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 71808

African (AFR) AF: 0.0000252 AC: 1 AN: 39746

American (AMR) AF: 0.00 AC: 0 AN: 14884

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3412

East Asian (EAS) AF: 0.00 AC: 0 AN: 4688

South Asian (SAS) AF: 0.00 AC: 0 AN: 4600

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 254

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66032

Other (OTH) AF: 0.00 AC: 0 AN: 1974

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000833 AC: 1

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	0.25
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.36	T
Eigen	Benign	-0.091
Eigen_PC	Benign	-0.018
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.74	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.23	T
MetaSVM	Uncertain	0.40	D
MutationAssessor	Benign	1.8	L
PhyloP100		3.0
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.35
Sift	Benign	0.13	T
Sift4G	Benign	0.28	T
Polyphen		0.39	B
Vest4		0.34
MutPred		0.25		Gain of glycosylation at R98 (P = 0.0166)
MVP		0.52
MPC		0.84
ClinPred		0.77	D
GERP RS		5.0
Varity_R		0.49
gMVP		0.79
Mutation Taster		=72/28	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: rs761171147; hg19: chr17-74136184;