rs17125470

Positions:

• chr14-89191523-G-A
• chr14-89191523-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005197.4(FOXN3):​c.746-10717C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0801 in 152,216 control chromosomes in the GnomAD database, including 643 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 0.080 (643 hom., cov: 31)
• Consequence: FOXN3 NM_005197.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.11

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXN3	NM_005197.4	c.746-10717C>T		intron_variant		ENST00000557258.6
FOXN3	NM_001085471.2	c.746-1074C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXN3	ENST00000557258.6	c.746-10717C>T		intron_variant		1	NM_005197.4	A1

Frequencies

GnomAD3 genomes AF: 0.0800 AC: 12166 AN: 152098 Hom.: 639 Cov.: 31

Gnomad AFR AF: 0.0333

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0963

Gnomad ASJ AF: 0.0504

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0764

Gnomad OTH AF: 0.0713

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

GnomAD4 genome AF: 0.0801 AC: 12187 AN: 152216 Hom.: 643 Cov.: 31 AF XY: 0.0868 AC XY: 6456 AN XY: 74412

Gnomad4 AFR AF: 0.0333

Gnomad4 AMR AF: 0.0969

Gnomad4 ASJ AF: 0.0504

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.0764

Gnomad4 OTH AF: 0.0777

Alfa AF: 0.0752 Hom.: 468

Bravo AF: 0.0741

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	15
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs17125470; hg19: chr14-89657867;