rs966834

chr14-89478405-A-C

Variant summary

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

The ENST00000345097.8(FOXN3):c.-14-65915T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0977 in 152,272 control chromosomes in the GnomAD database, including 851 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 0.098 (851 hom., cov: 30)
• Consequence: FOXN3 ENST00000345097.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.902

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXN3	NM_001085471.2	c.-14-65915T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXN3	ENST00000345097.8	c.-14-65915T>G		intron_variant		1		P4
FOXN3	ENST00000555353.5	c.-14-65915T>G		intron_variant		1		A1
FOXN3	ENST00000553904.1	c.-15+8164T>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0978 AC: 14875 AN: 152154 Hom.: 852 Cov.: 30

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0682

Gnomad ASJ AF: 0.0594

Gnomad EAS AF: 0.0310

Gnomad SAS AF: 0.0528

Gnomad FIN AF: 0.0678

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0819

Gnomad OTH AF: 0.0932

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

GnomAD4 genome AF: 0.0977 AC: 14882 AN: 152272 Hom.: 851 Cov.: 30 AF XY: 0.0957 AC XY: 7130 AN XY: 74466

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.0680

Gnomad4 ASJ AF: 0.0594

Gnomad4 EAS AF: 0.0309

Gnomad4 SAS AF: 0.0530

Gnomad4 FIN AF: 0.0678

Gnomad4 NFE AF: 0.0819

Gnomad4 OTH AF: 0.0918

Alfa AF: 0.0931 Hom.: 98

Bravo AF: 0.0996

Asia WGS AF: 0.0360 AC: 125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	7.0
Dann	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs966834; hg19: chr14-89944749;