rs585320

Variant names:

• chr1-42198567-T-C
• rs585320
• NM_014947.5:c.759+535A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014947.5(FOXJ3):​c.759+535A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,142 control chromosomes in the GnomAD database, including 2,856 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (2856 hom., cov: 32)
• Consequence: FOXJ3 NM_014947.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.594
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXJ3	NM_014947.5	c.759+535A>G		intron_variant	Intron 7 of 12	ENST00000361346.6	NP_055762.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXJ3	ENST00000361346.6	c.759+535A>G		intron_variant	Intron 7 of 12	1	NM_014947.5	ENSP00000354620.1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29006 AN: 152024 Hom.: 2855 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.164

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.191 AC: 29020 AN: 152142 Hom.: 2856 Cov.: 32 AF XY: 0.191 AC XY: 14233 AN XY: 74372

African (AFR) AF: 0.196 AC: 8151 AN: 41500

American (AMR) AF: 0.140 AC: 2149 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 473 AN: 3462

East Asian (EAS) AF: 0.175 AC: 908 AN: 5176

South Asian (SAS) AF: 0.252 AC: 1212 AN: 4818

European-Finnish (FIN) AF: 0.177 AC: 1873 AN: 10590

Middle Eastern (MID) AF: 0.168 AC: 49 AN: 292

European-Non Finnish (NFE) AF: 0.201 AC: 13667 AN: 67982

Other (OTH) AF: 0.165 AC: 349 AN: 2112

Alfa AF: 0.188 Hom.: 3527

Bravo AF: 0.184

Asia WGS AF: 0.257 AC: 893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.6
DANN	Benign	0.58
PhyloP100		-0.59
Mutation Taster		=100/0	polymorphism (auto)

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: rs585320; hg19: chr1-42664238;