rs741272

Positions:

• chr14-89399608-T-C

Variant summary

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

The ENST00000557258.6(FOXN3):​c.543+12326A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,144 control chromosomes in the GnomAD database, including 13,051 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 0.37 (13051 hom., cov: 32)
• Consequence: FOXN3 ENST00000557258.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.512

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXN3	NM_005197.4	c.543+12326A>G		intron_variant		ENST00000557258.6	NP_005188.2
FOXN3	NM_001085471.2	c.543+12326A>G		intron_variant			NP_001078940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXN3	ENST00000557258.6	c.543+12326A>G		intron_variant		1	NM_005197.4	ENSP00000452005	A1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56443 AN: 152026 Hom.: 13045 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.371 AC: 56451 AN: 152144 Hom.: 13051 Cov.: 32 AF XY: 0.380 AC XY: 28212 AN XY: 74334

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.520

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.618

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.354

Alfa AF: 0.433 Hom.: 2744

Bravo AF: 0.352

Asia WGS AF: 0.280 AC: 973 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.57

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: rs741272; hg19: chr14-89865952;