Variant 1-42191392-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014947.5(FOXJ3):c.1262A>G(p.His421Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,454,802 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 (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

FOXJ3
NM_014947.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.23

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]

FOXJ3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3923644).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXJ3	NM_014947.5 linkuse as main transcript	c.1262A>G	p.His421Arg	missense_variant	9/13	ENST00000361346.6	NP_055762.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXJ3	ENST00000361346.6 linkuse as main transcript	c.1262A>G	p.His421Arg	missense_variant	9/13	1	NM_014947.5	ENSP00000354620	P1	Q9UPW0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1454802

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723492

show subpopulations

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:

9.04e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 12, 2022

The c.1262A>G (p.H421R) alteration is located in exon 11 (coding exon 8) of the FOXJ3 gene. This alteration results from a A to G substitution at nucleotide position 1262, causing the histidine (H) at amino acid position 421 to be replaced by an arginine (R). 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

0.20

BayesDel_addAF

Uncertain

0.061

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.083

T;T;T;.;T

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.87

.;.;.;D;D

M_CAP

Benign

0.0087

MetaRNN

Benign

0.39

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;L;L;.;L

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.69

N;N;N;N;N

REVEL

Benign

0.15

Sift

Uncertain

0.0030

D;D;D;D;D

Sift4G

Benign

0.81

T;T;T;T;T

Polyphen

0.60

P;P;P;P;P

Vest4

0.56

MutPred

0.32

Gain of catalytic residue at H421 (P = 0.0435);Gain of catalytic residue at H421 (P = 0.0435);Gain of catalytic residue at H421 (P = 0.0435);.;Gain of catalytic residue at H421 (P = 0.0435);

MVP

0.60

MPC

0.99

ClinPred

0.71

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.35

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over