Variant 11-125452358-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005103.5(FEZ1):c.1072G>C(p.Glu358Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0147 in 1,612,482 control chromosomes in the GnomAD database, including 223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 11 hom., cov: 32)

Exomes 𝑓: 0.015 ( 212 hom. )

Consequence

FEZ1
NM_005103.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.42

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008377522).

BP6

Variant 11-125452358-C-G is Benign according to our data. Variant chr11-125452358-C-G is described in ClinVar as [Benign]. Clinvar id is 786218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.011 (1673/152266) while in subpopulation NFE AF= 0.0172 (1171/68018). AF 95% confidence interval is 0.0164. There are 11 homozygotes in gnomad4. There are 755 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FEZ1	NM_005103.5 linkuse as main transcript	c.1072G>C	p.Glu358Gln	missense_variant	8/10	ENST00000278919.8
FEZ1	XM_005271734.3 linkuse as main transcript	c.1072G>C	p.Glu358Gln	missense_variant	8/10
FEZ1	XM_005271735.3 linkuse as main transcript	c.1072G>C	p.Glu358Gln	missense_variant	8/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FEZ1	ENST00000278919.8 linkuse as main transcript	c.1072G>C	p.Glu358Gln	missense_variant	8/10	1	NM_005103.5	P1	Q99689-1

Frequencies

GnomAD3 genomes

AF:

0.0110

AC:

1674

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00299

Gnomad AMI

AF:

0.0363

Gnomad AMR

AF:

0.00767

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0158

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0172

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.0103

AC:

2595

AN:

251432

Hom.:

AF XY:

0.0103

AC XY:

1406

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.00344

Gnomad AMR exome

AF:

0.00321

Gnomad ASJ exome

AF:

0.0121

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00186

Gnomad FIN exome

AF:

0.0182

Gnomad NFE exome

AF:

0.0157

Gnomad OTH exome

AF:

0.0104

GnomAD4 exome

AF:

0.0151

AC:

22030

AN:

1460216

Hom.:

212

Cov.:

AF XY:

0.0148

AC XY:

10735

AN XY:

726584

show subpopulations

Gnomad4 AFR exome

AF:

0.00239

Gnomad4 AMR exome

AF:

0.00382

Gnomad4 ASJ exome

AF:

0.0115

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00201

Gnomad4 FIN exome

AF:

0.0178

Gnomad4 NFE exome

AF:

0.0176

Gnomad4 OTH exome

AF:

0.0124

GnomAD4 genome

AF:

0.0110

AC:

1673

AN:

152266

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

755

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00298

Gnomad4 AMR

AF:

0.00766

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.0158

Gnomad4 NFE

AF:

0.0172

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.0148

Hom.:

Bravo

AF:

0.0102

TwinsUK

AF:

0.0200

AC:

ALSPAC

AF:

0.0236

AC:

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.0166

AC:

143

ExAC

AF:

0.00978

AC:

1187

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0164

EpiControl

AF:

0.0136

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.62

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

T;T

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.89

.;D

MetaRNN

Benign

0.0084

T;T

MetaSVM

Benign

-0.73

MutationAssessor

Benign

1.1

L;L

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.90

.;N

REVEL

Benign

0.10

Sift

Benign

0.52

.;T

Sift4G

Benign

0.52

.;T

Polyphen

0.85

P;P

Vest4

0.37

MPC

0.70

ClinPred

0.015

GERP RS

5.0

Varity_R

0.40

gMVP

0.37

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over