Variant 11-125481576-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005103.5(FEZ1):c.369T>A(p.Asp123Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,611,700 control chromosomes in the GnomAD database, including 26,699 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.19 ( 2762 hom., cov: 32)

Exomes 𝑓: 0.18 ( 23937 hom. )

Consequence

FEZ1
NM_005103.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.30

Variant links:

Genes affected

FEZ1 (HGNC:3659): (fasciculation and elongation protein zeta 1) This gene is an ortholog of the C. elegans unc-76 gene, which is necessary for normal axonal bundling and elongation within axon bundles. Expression of this gene in C. elegans unc-76 mutants can restore to the mutants partial locomotion and axonal fasciculation, suggesting that it also functions in axonal outgrowth. The N-terminal half of the gene product is highly acidic. Alternatively spliced transcript variants encoding different isoforms of this protein have been described. [provided by RefSeq, Jul 2008]

FEZ1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013558865).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FEZ1	NM_005103.5 linkuse as main transcript	c.369T>A	p.Asp123Glu	missense_variant	3/10	ENST00000278919.8
FEZ1	XM_005271734.3 linkuse as main transcript	c.369T>A	p.Asp123Glu	missense_variant	3/10
FEZ1	XM_005271735.3 linkuse as main transcript	c.369T>A	p.Asp123Glu	missense_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FEZ1	ENST00000278919.8 linkuse as main transcript	c.369T>A	p.Asp123Glu	missense_variant	3/10	1	NM_005103.5	P1	Q99689-1

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28186

AN:

152018

Hom.:

2756

Cov.:

show subpopulations

Gnomad AFR

AF:

0.218

Gnomad AMI

AF:

0.334

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.0709

Gnomad SAS

AF:

0.0763

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.183

Gnomad OTH

AF:

0.182

GnomAD3 exomes

AF:

0.154

AC:

38686

AN:

251410

Hom.:

3447

AF XY:

0.151

AC XY:

20461

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.215

Gnomad AMR exome

AF:

0.108

Gnomad ASJ exome

AF:

0.159

Gnomad EAS exome

AF:

0.0637

Gnomad SAS exome

AF:

0.0714

Gnomad FIN exome

AF:

0.228

Gnomad NFE exome

AF:

0.181

Gnomad OTH exome

AF:

0.154

GnomAD4 exome

AF:

0.176

AC:

256516

AN:

1459564

Hom.:

23937

Cov.:

AF XY:

0.173

AC XY:

125489

AN XY:

726242

show subpopulations

Gnomad4 AFR exome

AF:

0.221

Gnomad4 AMR exome

AF:

0.112

Gnomad4 ASJ exome

AF:

0.166

Gnomad4 EAS exome

AF:

0.0797

Gnomad4 SAS exome

AF:

0.0717

Gnomad4 FIN exome

AF:

0.227

Gnomad4 NFE exome

AF:

0.187

Gnomad4 OTH exome

AF:

0.171

GnomAD4 genome

AF:

0.185

AC:

28220

AN:

152136

Hom.:

2762

Cov.:

AF XY:

0.184

AC XY:

13674

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.218

Gnomad4 AMR

AF:

0.137

Gnomad4 ASJ

AF:

0.184

Gnomad4 EAS

AF:

0.0710

Gnomad4 SAS

AF:

0.0768

Gnomad4 FIN

AF:

0.237

Gnomad4 NFE

AF:

0.183

Gnomad4 OTH

AF:

0.180

Alfa

AF:

0.177

Hom.:

1823

Bravo

AF:

0.182

TwinsUK

AF:

0.200

AC:

742

ALSPAC

AF:

0.208

AC:

803

ESP6500AA

AF:

0.216

AC:

951

ESP6500EA

AF:

0.186

AC:

1601

ExAC

AF:

0.157

AC:

18999

Asia WGS

AF:

0.0940

AC:

327

AN:

3478

EpiCase

AF:

0.177

EpiControl

AF:

0.184

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.099

T;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.44

.;T

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

0.0051

PrimateAI

Benign

0.40

PROVEAN

Benign

0.17

.;N

REVEL

Benign

0.019

Sift

Benign

0.40

.;T

Sift4G

Benign

1.0

.;T

Polyphen

0.13

B;B

Vest4

0.085

MutPred

0.36

Gain of helix (P = 0.062);Gain of helix (P = 0.062);

MPC

0.36

ClinPred

0.014

GERP RS

3.0

Varity_R

0.053

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over