1-42179780-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014947.5(FOXJ3):c.1799C>G(p.Ala600Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: FOXJ3 NM_014947.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.26

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09395966).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXJ3	NM_014947.5	c.1799C>G	p.Ala600Gly	missense_variant	13/13	ENST00000361346.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXJ3	ENST00000361346.6	c.1799C>G	p.Ala600Gly	missense_variant	13/13	1	NM_014947.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

The c.1799C>G (p.A600G) alteration is located in exon 15 (coding exon 12) of the FOXJ3 gene. This alteration results from a C to G substitution at nucleotide position 1799, causing the alanine (A) at amino acid position 600 to be replaced by a glycine (G). 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	0.084
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
Cadd	Benign	22
Dann	Uncertain	0.98
DEOGEN2	Benign	0.013	T;T;T;T;.;T
Eigen	Benign	-0.038
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.90	D;.;.;.;D;D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.094	T;T;T;T;T;T
MetaSVM	Uncertain	-0.043	T
MutationTaster	Benign	0.95	D;D;D;D;D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.32	N;N;N;N;N;N
REVEL	Uncertain	0.29
Sift	Benign	0.67	T;T;T;T;T;T
Sift4G	Benign	0.26	T;T;T;T;T;T
Polyphen		0.13	.;B;B;B;.;B
Vest4		0.17
MutPred		0.16		.;Loss of glycosylation at P597 (P = 0.1801);Loss of glycosylation at P597 (P = 0.1801);Loss of glycosylation at P597 (P = 0.1801);.;Loss of glycosylation at P597 (P = 0.1801);
MVP		0.35
MPC		0.26
ClinPred		0.75	D
GERP RS		5.8
Varity_R		0.11
gMVP		0.37

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: chr1-42645451;