14-89191523-G-A

Variant names:

• chr14-89191523-G-A
• rs17125470
• NM_005197.4:c.746-10717C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005197.4(FOXN3):​c.746-10717C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0801 in 152,216 control chromosomes in the GnomAD database, including 643 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 0.080 (643 hom., cov: 31)
• Consequence: FOXN3 NM_005197.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.11
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005197.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXN3	NM_005197.4	MANE Select	c.746-10717C>T		intron	N/A	NP_005188.2
	FOXN3	NM_001085471.2		c.746-1074C>T		intron	N/A	NP_001078940.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXN3	ENST00000557258.6	TSL:1 MANE Select	c.746-10717C>T		intron	N/A	ENSP00000452005.1
	FOXN3	ENST00000345097.8	TSL:1	c.746-1074C>T		intron	N/A	ENSP00000343288.4
	FOXN3	ENST00000555353.5	TSL:1	c.746-10717C>T		intron	N/A	ENSP00000452227.1

Frequencies

GnomAD3 genomes AF: 0.0800 AC: 12166 AN: 152098 Hom.: 639 Cov.: 31

Gnomad AFR AF: 0.0333

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0963

Gnomad ASJ AF: 0.0504

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0764

Gnomad OTH AF: 0.0713

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

GnomAD4 genome AF: 0.0801 AC: 12187 AN: 152216 Hom.: 643 Cov.: 31 AF XY: 0.0868 AC XY: 6456 AN XY: 74412

African (AFR) AF: 0.0333 AC: 1382 AN: 41542

American (AMR) AF: 0.0969 AC: 1482 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0504 AC: 175 AN: 3472

East Asian (EAS) AF: 0.263 AC: 1358 AN: 5166

South Asian (SAS) AF: 0.155 AC: 747 AN: 4832

European-Finnish (FIN) AF: 0.155 AC: 1637 AN: 10578

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0764 AC: 5194 AN: 68008

Other (OTH) AF: 0.0777 AC: 164 AN: 2112

Alfa AF: 0.0760 Hom.: 727

Bravo AF: 0.0741

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	15
DANN	Benign	0.82
PhyloP100		3.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17125470; hg19: chr14-89657867;