1-42182002-C-A

Variant names:

• chr1-42182002-C-A
• NM_014947.5:c.1668G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014947.5(FOXJ3):​c.1668G>T​(p.Arg556Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 3.11
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014947.5. 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
	FOXJ3	NM_014947.5	MANE Select	c.1668G>T	p.Arg556Ser	missense	Exon 12 of 13	NP_055762.3
	FOXJ3	NM_001198850.2		c.1668G>T	p.Arg556Ser	missense	Exon 12 of 13	NP_001185779.1	Q9UPW0-1
	FOXJ3	NM_001198851.2		c.1668G>T	p.Arg556Ser	missense	Exon 14 of 15	NP_001185780.1	Q9UPW0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXJ3	ENST00000361346.6	TSL:1 MANE Select	c.1668G>T	p.Arg556Ser	missense	Exon 12 of 13	ENSP00000354620.1	Q9UPW0-1
	FOXJ3	ENST00000372572.5	TSL:1	c.1668G>T	p.Arg556Ser	missense	Exon 14 of 15	ENSP00000361653.1	Q9UPW0-1
	FOXJ3	ENST00000372573.5	TSL:2	c.1668G>T	p.Arg556Ser	missense	Exon 12 of 13	ENSP00000361654.1	Q9UPW0-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.044	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.069	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Uncertain	0.79	D
MutationAssessor	Benign	1.9	L
PhyloP100		3.1
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.46
Sift	Benign	0.053	T
Sift4G	Benign	0.21	T
Polyphen		0.98	D
Vest4		0.77
MutPred		0.17		Loss of catalytic residue at R556 (P = 0.0155)
MVP		0.82
MPC		0.34
ClinPred		0.81	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.70
Mutation Taster		=49/51	disease causing

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

hg19: chr1-42647673;