rs243196

chr14-89577037-C-Achr14-89577037-C-Gchr14-89577037-C-T

Variant summary

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

The ENST00000345097.8(FOXN3):c.-15+41991G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.891 in 152,168 control chromosomes in the GnomAD database, including 60,764 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 0.89 (60763 hom., cov: 32)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: FOXN3 ENST00000345097.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236

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]

FOXN3-AS2 (HGNC:30119): (FOXN3 antisense RNA 2)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXN3-AS2	NR_024620.1	n.822C>A		non_coding_transcript_exon_variant	1/1
FOXN3	NM_001085471.2	c.-15+41991G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXN3	ENST00000345097.8	c.-15+41991G>T		intron_variant		1		P4
FOXN3	ENST00000555353.5	c.-15+41991G>T		intron_variant		1		A1
FOXN3-AS2	ENST00000554071.1	n.822C>A		non_coding_transcript_exon_variant	1/1
FOXN3	ENST00000555855.5	c.-118+41991G>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.891 AC: 135469 AN: 152048 Hom.: 60710 Cov.: 32

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.915

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.906

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.891

Gnomad OTH AF: 0.883

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 FIN exome AF: 1.00

GnomAD4 genome AF: 0.891 AC: 135574 AN: 152166 Hom.: 60763 Cov.: 32 AF XY: 0.888 AC XY: 66079 AN XY: 74372

Gnomad4 AFR AF: 0.938

Gnomad4 AMR AF: 0.915

Gnomad4 ASJ AF: 0.778

Gnomad4 EAS AF: 0.627

Gnomad4 SAS AF: 0.765

Gnomad4 FIN AF: 0.906

Gnomad4 NFE AF: 0.891

Gnomad4 OTH AF: 0.872

Alfa AF: 0.881 Hom.: 76307

Bravo AF: 0.894

Asia WGS AF: 0.667 AC: 2323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	1.5
Dann	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs243196; hg19: chr14-90043381;