ENST00000345097.8:c.-15+90109T>C

Variant names:

• chr14-89528919-A-G
• rs373655
• ENST00000345097.8:c.-15+90109T>C

Variant summary

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

The ENST00000345097.8(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 ENST00000345097.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000345097.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXN3	NM_001085471.2		c.-15+90109T>C		intron	N/A	NP_001078940.1	O00409-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXN3	ENST00000345097.8	TSL:1	c.-15+90109T>C		intron	N/A	ENSP00000343288.4	O00409-1
	FOXN3	ENST00000555353.5	TSL:1	c.-15+90109T>C		intron	N/A	ENSP00000452227.1	O00409-2
	FOXN3	ENST00000884418.1		c.-114-42251T>C		intron	N/A	ENSP00000554477.1

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

African (AFR) AF: 0.789 AC: 32692 AN: 41424

American (AMR) AF: 0.569 AC: 8688 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.681 AC: 2364 AN: 3472

East Asian (EAS) AF: 0.832 AC: 4308 AN: 5180

South Asian (SAS) AF: 0.678 AC: 3267 AN: 4822

European-Finnish (FIN) AF: 0.583 AC: 6142 AN: 10534

Middle Eastern (MID) AF: 0.586 AC: 171 AN: 292

European-Non Finnish (NFE) AF: 0.579 AC: 39315 AN: 67956

Other (OTH) AF: 0.663 AC: 1398 AN: 2110

Alfa AF: 0.597 Hom.: 24279

Bravo AF: 0.656

Asia WGS AF: 0.787 AC: 2736 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.32
DANN	Benign	0.24
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs373655;

hg19: chr14-89995263;