NM_005197.4:c.681-11253C>T

Variant names:

• chr14-89292267-G-A
• rs759364
• NM_005197.4:c.681-11253C>T

Variant summary

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

The NM_005197.4(FOXN3):​c.681-11253C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 151,822 control chromosomes in the GnomAD database, including 4,500 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 0.24 (4500 hom., cov: 31)
• Consequence: FOXN3 NM_005197.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.315 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXN3	NM_005197.4	MANE Select	c.681-11253C>T		intron	N/A	NP_005188.2	O00409-2
	FOXN3	NM_001085471.2		c.681-11253C>T		intron	N/A	NP_001078940.1	O00409-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXN3	ENST00000557258.6	TSL:1 MANE Select	c.681-11253C>T		intron	N/A	ENSP00000452005.1	O00409-2
	FOXN3	ENST00000345097.8	TSL:1	c.681-11253C>T		intron	N/A	ENSP00000343288.4	O00409-1
	FOXN3	ENST00000555353.5	TSL:1	c.681-11253C>T		intron	N/A	ENSP00000452227.1	O00409-2

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36723 AN: 151704 Hom.: 4485 Cov.: 31

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.242 AC: 36778 AN: 151822 Hom.: 4500 Cov.: 31 AF XY: 0.245 AC XY: 18150 AN XY: 74188

African (AFR) AF: 0.236 AC: 9756 AN: 41354

American (AMR) AF: 0.323 AC: 4920 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 623 AN: 3470

East Asian (EAS) AF: 0.274 AC: 1413 AN: 5152

South Asian (SAS) AF: 0.307 AC: 1477 AN: 4810

European-Finnish (FIN) AF: 0.212 AC: 2227 AN: 10518

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15709 AN: 67950

Other (OTH) AF: 0.211 AC: 446 AN: 2112

Alfa AF: 0.242 Hom.: 4852

Bravo AF: 0.248

Asia WGS AF: 0.312 AC: 1087 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.12
DANN	Benign	0.63
PhyloP100		-1.4
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: rs759364; hg19: chr14-89758611; COSMIC: COSV54305074; COSMIC: COSV54305074;