1-42191406-C-G

Variant names:

• chr1-42191406-C-G
• rs138136512
• NM_014947.5:c.1248G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014947.5(FOXJ3):​c.1248G>C​(p.Gln416His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FOXJ3 NM_014947.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.863
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.233268).

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.1248G>C	p.Gln416His	missense	Exon 9 of 13	NP_055762.3
	FOXJ3	NM_001198850.2		c.1248G>C	p.Gln416His	missense	Exon 9 of 13	NP_001185779.1	Q9UPW0-1
	FOXJ3	NM_001198851.2		c.1248G>C	p.Gln416His	missense	Exon 11 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.1248G>C	p.Gln416His	missense	Exon 9 of 13	ENSP00000354620.1	Q9UPW0-1
	FOXJ3	ENST00000372572.5	TSL:1	c.1248G>C	p.Gln416His	missense	Exon 11 of 15	ENSP00000361653.1	Q9UPW0-1
	FOXJ3	ENST00000445886.5	TSL:1	c.1146G>C	p.Gln382His	missense splice_region	Exon 8 of 8	ENSP00000393408.1	C9JVP0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	Benign	0.14
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.086	T
Eigen	Benign	-0.076
Eigen_PC	Benign	0.016
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.19	T
MetaSVM	Uncertain	-0.095	T
MutationAssessor	Benign	0.46	N
PhyloP100		0.86
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.77	N
REVEL	Benign	0.14
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.38	T
Polyphen		0.65	P
Vest4		0.43
MutPred		0.22		Gain of glycosylation at P415 (P = 0.0571)
MVP		0.79
MPC		0.42
ClinPred		0.47	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.49
Mutation Taster		=84/16	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: rs138136512; hg19: chr1-42657077;