rs138136512

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-42191406-C-A
• chr1-42191406-C-G
• chr1-42191406-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_014947.5(FOXJ3):​c.1248G>T​(p.Gln416His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000188 in 1,608,856 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (0 hom.)
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.21446022).
• BS2: High AC in GnomAd4 at 6 AD gene.

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

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 151906 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000736

Gnomad OTH AF: 0.000481

GnomAD2 exomes AF: 0.0000200 AC: 5 AN: 249656 AF XY: 0.0000297

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000444

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000203 AC: 296 AN: 1456832 Hom.: 0 Cov.: 30 AF XY: 0.000203 AC XY: 147 AN XY: 724664

African (AFR) AF: 0.0000300 AC: 1 AN: 33382

American (AMR) AF: 0.00 AC: 0 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25982

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.00 AC: 0 AN: 85922

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53366

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.000265 AC: 294 AN: 1107856

Other (OTH) AF: 0.0000166 AC: 1 AN: 60256

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 152024 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74314

African (AFR) AF: 0.00 AC: 0 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67970

Other (OTH) AF: 0.000476 AC: 1 AN: 2100

Alfa AF: 0.0000225 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.000218

EpiControl AF: 0.00

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	0.065	T
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	0.87	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.17	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		0.21	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;