rs597570

Variant summary

Our verdict is Benign. The variant received -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. 14/22 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.19 ( 2762 hom., cov: 32)
Exomes 𝑓: 0.18 ( 23937 hom. )

Consequence

FEZ1
NM_005103.5 missense

Scores

2
16

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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank MANE Protein UniProt
FEZ1NM_005103.5 linkc.369T>A p.Asp123Glu missense_variant Exon 3 of 10 ENST00000278919.8 NP_005094.1 Q99689-1
FEZ1XM_005271734.3 linkc.369T>A p.Asp123Glu missense_variant Exon 3 of 10 XP_005271791.1 Q99689-1
FEZ1XM_005271735.3 linkc.369T>A p.Asp123Glu missense_variant Exon 3 of 10 XP_005271792.1 Q99689-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FEZ1ENST00000278919.8 linkc.369T>A p.Asp123Glu missense_variant Exon 3 of 10 1 NM_005103.5 ENSP00000278919.3 Q99689-1

Frequencies

GnomAD3 genomes
AF:
0.185
AC:
28186
AN:
152018
Hom.:
2756
Cov.:
32
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
GnomAD2 exomes
AF:
0.154
AC:
38686
AN:
251410
AF XY:
0.151
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 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.:
30
AF XY:
0.173
AC XY:
125489
AN XY:
726242
show subpopulations
Gnomad4 AFR exome
AF:
0.221
AC:
7374
AN:
33418
Gnomad4 AMR exome
AF:
0.112
AC:
5023
AN:
44720
Gnomad4 ASJ exome
AF:
0.166
AC:
4338
AN:
26124
Gnomad4 EAS exome
AF:
0.0797
AC:
3163
AN:
39694
Gnomad4 SAS exome
AF:
0.0717
AC:
6186
AN:
86222
Gnomad4 FIN exome
AF:
0.227
AC:
12111
AN:
53416
Gnomad4 NFE exome
AF:
0.187
AC:
207088
AN:
1110092
Gnomad4 Remaining exome
AF:
0.171
AC:
10308
AN:
60292
Heterozygous variant carriers
0
10068
20136
30204
40272
50340
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
7222
14444
21666
28888
36110
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.185
AC:
28220
AN:
152136
Hom.:
2762
Cov.:
32
AF XY:
0.184
AC XY:
13674
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.218
AC:
0.217849
AN:
0.217849
Gnomad4 AMR
AF:
0.137
AC:
0.13656
AN:
0.13656
Gnomad4 ASJ
AF:
0.184
AC:
0.183862
AN:
0.183862
Gnomad4 EAS
AF:
0.0710
AC:
0.0710425
AN:
0.0710425
Gnomad4 SAS
AF:
0.0768
AC:
0.0767954
AN:
0.0767954
Gnomad4 FIN
AF:
0.237
AC:
0.237101
AN:
0.237101
Gnomad4 NFE
AF:
0.183
AC:
0.183381
AN:
0.183381
Gnomad4 OTH
AF:
0.180
AC:
0.179754
AN:
0.179754
Heterozygous variant carriers
0
1202
2404
3606
4808
6010
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
290
580
870
1160
1450
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
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
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
15
DANN
Uncertain
0.98
DEOGEN2
Benign
0.099
T;T
Eigen
Benign
-0.31
Eigen_PC
Benign
-0.17
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Benign
0.44
.;T
MetaRNN
Benign
0.0014
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L;L
PrimateAI
Benign
0.40
T
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
T
GERP RS
3.0
Varity_R
0.053
gMVP
0.12
Mutation Taster
=95/5
polymorphism (auto)

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.

Other links and lift over

dbSNP: rs597570; hg19: chr11-125351472; COSMIC: COSV54030673; API