14-89412326-C-T

Position:

• chr14-89412326-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000557258.6(FOXN3):​c.151G>A​(p.Glu51Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: FOXN3 ENST00000557258.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.04

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17871326).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXN3	NM_005197.4	c.151G>A	p.Glu51Lys	missense_variant	2/6	ENST00000557258.6	NP_005188.2
FOXN3	NM_001085471.2	c.151G>A	p.Glu51Lys	missense_variant	2/7		NP_001078940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXN3	ENST00000557258.6	c.151G>A	p.Glu51Lys	missense_variant	2/6	1	NM_005197.4	ENSP00000452005	A1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2024

The c.151G>A (p.E51K) alteration is located in exon 2 (coding exon 1) of the FOXN3 gene. This alteration results from a G to A substitution at nucleotide position 151, causing the glutamic acid (E) at amino acid position 51 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;T;.;.;.;T;T;.
Eigen	Benign	-0.17
Eigen_PC	Benign	0.035
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.78	.;T;.;T;.;T;T;T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.18	T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.20	D
MutationAssessor	Benign	0.74	N;N;N;N;N;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.89	N;N;N;.;N;N;N;D
REVEL	Benign	0.11
Sift	Benign	0.25	T;T;T;.;T;T;T;D
Sift4G	Benign	0.90	T;T;T;T;T;T;.;.
Polyphen		0.0020	B;B;B;B;B;.;.;.
Vest4		0.22
MutPred		0.41		Gain of ubiquitination at E51 (P = 0.0066);Gain of ubiquitination at E51 (P = 0.0066);Gain of ubiquitination at E51 (P = 0.0066);Gain of ubiquitination at E51 (P = 0.0066);Gain of ubiquitination at E51 (P = 0.0066);Gain of ubiquitination at E51 (P = 0.0066);Gain of ubiquitination at E51 (P = 0.0066);Gain of ubiquitination at E51 (P = 0.0066);
MVP		0.75
MPC		0.40
ClinPred		0.40	T
GERP RS		5.2
Varity_R		0.13
gMVP		0.53

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-89878670;