rs8006194

chr14-89444509-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000345097.8(FOXN3):c.-14-32019G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,594 control chromosomes in the GnomAD database, including 18,777 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 0.49 (18777 hom., cov: 31)
• Consequence: FOXN3 ENST00000345097.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.512

Genes affected

FOXN3 (HGNC:1928): (forkhead box N3) This gene is a member of the forkhead/winged helix transcription factor family. Checkpoints are eukaryotic DNA damage-inducible cell cycle arrests at G1 and G2. Checkpoint suppressor 1 suppresses multiple yeast checkpoint mutations including mec1, rad9, rad53 and dun1 by activating a MEC1-independent checkpoint pathway. Alternative splicing is observed at the locus, resulting in distinct isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXN3	NM_001085471.2	c.-14-32019G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXN3	ENST00000345097.8	c.-14-32019G>T		intron_variant		1		P4
FOXN3	ENST00000555353.5	c.-14-32019G>T		intron_variant		1		A1
FOXN3	ENST00000553904.1	c.-14-32019G>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73769 AN: 151486 Hom.: 18763 Cov.: 31

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.635

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.487 AC: 73806 AN: 151594 Hom.: 18777 Cov.: 31 AF XY: 0.491 AC XY: 36372 AN XY: 74054

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.625

Gnomad4 ASJ AF: 0.536

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.535

Alfa AF: 0.505 Hom.: 3573

Bravo AF: 0.491

Asia WGS AF: 0.456 AC: 1591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	13
Dann	Benign	0.90

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs8006194; hg19: chr14-89910853;