1-42179814-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014947.5(FOXJ3):​c.1765G>T​(p.Ala589Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

FOXJ3
NM_014947.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.09
Variant links:
Genes affected
FOXJ3 (HGNC:29178): (forkhead box J3) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and sequence-specific double-stranded DNA binding activity. Involved in positive regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.059868604).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FOXJ3NM_014947.5 linkc.1765G>T p.Ala589Ser missense_variant Exon 13 of 13 ENST00000361346.6 NP_055762.3 Q9UPW0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FOXJ3ENST00000361346.6 linkc.1765G>T p.Ala589Ser missense_variant Exon 13 of 13 1 NM_014947.5 ENSP00000354620.1 Q9UPW0-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152122
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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
GnomAD4 exome
Cov.:
29
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152122
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000264

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 14, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1765G>T (p.A589S) alteration is located in exon 15 (coding exon 12) of the FOXJ3 gene. This alteration results from a G to T substitution at nucleotide position 1765, causing the alanine (A) at amino acid position 589 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.076
BayesDel_addAF
Uncertain
0.029
T
BayesDel_noAF
Benign
-0.20
CADD
Benign
15
DANN
Benign
0.95
DEOGEN2
Benign
0.0085
T;T;T;T;.;T
Eigen
Benign
-0.40
Eigen_PC
Benign
-0.19
FATHMM_MKL
Benign
0.67
D
LIST_S2
Uncertain
0.92
D;.;.;.;D;D
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.060
T;T;T;T;T;T
MetaSVM
Uncertain
-0.28
T
MutationAssessor
Benign
0.34
.;N;N;N;.;N
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-0.29
N;N;N;N;N;N
REVEL
Benign
0.25
Sift
Benign
0.97
T;T;T;T;T;T
Sift4G
Benign
0.78
T;T;T;T;T;T
Polyphen
0.13
.;B;B;B;.;B
Vest4
0.12
MutPred
0.13
.;Gain of phosphorylation at A589 (P = 0.099);Gain of phosphorylation at A589 (P = 0.099);Gain of phosphorylation at A589 (P = 0.099);.;Gain of phosphorylation at A589 (P = 0.099);
MVP
0.36
MPC
0.24
ClinPred
0.51
D
GERP RS
3.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.045
gMVP
0.42

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs900658196; hg19: chr1-42645485; API