14-89528919-A-G

Position:

• chr14-89528919-A-G

Variant summary

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

The NM_001085471.2(FOXN3):​c.-15+90109T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 151,970 control chromosomes in the GnomAD database, including 32,930 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 0.65 (32930 hom., cov: 31)
• Consequence: FOXN3 NM_001085471.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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]

ENSG00000259053 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXN3	NM_001085471.2	c.-15+90109T>C		intron_variant			NP_001078940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXN3	ENST00000345097.8	c.-15+90109T>C		intron_variant		1		ENSP00000343288.4
FOXN3	ENST00000555353.5	c.-15+90109T>C		intron_variant		1		ENSP00000452227.1
FOXN3	ENST00000555855.5	c.-117-42248T>C		intron_variant		5		ENSP00000451135.1
ENSG00000259053	ENST00000555070.1	n.171-42248T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98703 AN: 151852 Hom.: 32878 Cov.: 31

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.832

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.658

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

GnomAD4 genome AF: 0.650 AC: 98812 AN: 151970 Hom.: 32930 Cov.: 31 AF XY: 0.650 AC XY: 48261 AN XY: 74266

Gnomad4 AFR AF: 0.789

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.681

Gnomad4 EAS AF: 0.832

Gnomad4 SAS AF: 0.678

Gnomad4 FIN AF: 0.583

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.663

Alfa AF: 0.588 Hom.: 14512

Bravo AF: 0.656

Asia WGS AF: 0.787 AC: 2736 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.32
DANN	Benign	0.24

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs373655; hg19: chr14-89995263;