Variant 3-62372510-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_018008.4(FEZF2):c.359T>G(p.Val120Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000244 in 1,338,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

FEZF2
NM_018008.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.08

Variant links:

Genes affected

FEZF2 (HGNC:13506): (FEZ family zinc finger 2) Predicted to enable transcription cis-regulatory region binding activity. Predicted to be involved in positive regulation of transcription, DNA-templated. Predicted to act upstream of or within several processes, including negative regulation of transcription by RNA polymerase II; nervous system development; and regulation of neuron differentiation. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FEZF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0661107).

BS2

High AC in GnomAd4 at 24 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FEZF2	NM_018008.4 linkuse as main transcript	c.359T>G	p.Val120Gly	missense_variant	2/5	ENST00000283268.8	NP_060478.3	Q8TBJ5-1A0A140VKG3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FEZF2	ENST00000283268.8 linkuse as main transcript	c.359T>G	p.Val120Gly	missense_variant	2/5	1	NM_018008.4	ENSP00000283268.3	Q8TBJ5-1
FEZF2	ENST00000475839.1 linkuse as main transcript	c.359T>G	p.Val120Gly	missense_variant	1/4	1		ENSP00000418804.1	Q8TBJ5-1
FEZF2	ENST00000486811.5 linkuse as main transcript	c.359T>G	p.Val120Gly	missense_variant	3/6	5		ENSP00000418589.1	Q8TBJ5-1

Frequencies

GnomAD3 genomes

AF:

0.000160

AC:

AN:

150258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000265

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000282

Gnomad OTH

AF:

0.000486

GnomAD3 exomes

AF:

0.000123

AC:

AN:

56684

Hom.:

AF XY:

0.000151

AC XY:

AN XY:

33020

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000239

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000253

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000254

AC:

302

AN:

1188208

Hom.:

Cov.:

AF XY:

0.000253

AC XY:

146

AN XY:

576532

show subpopulations

Gnomad4 AFR exome

AF:

0.0000800

Gnomad4 AMR exome

AF:

0.0000709

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000296

Gnomad4 OTH exome

AF:

0.000187

GnomAD4 genome

AF:

0.000160

AC:

AN:

150358

Hom.:

Cov.:

AF XY:

0.000163

AC XY:

AN XY:

73466

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000264

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000282

Gnomad4 OTH

AF:

0.000481

Alfa

AF:

0.000270

Hom.:

Bravo

AF:

0.000178

ExAC

AF:

0.0000716

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 06, 2022

The c.359T>G (p.V120G) alteration is located in exon 2 (coding exon 1) of the FEZF2 gene. This alteration results from a T to G substitution at nucleotide position 359, causing the valine (V) at amino acid position 120 to be replaced by a glycine (G). 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

0.17

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.16

T;T;T

Eigen

Benign

-0.16

Eigen_PC

Benign

0.048

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.39

.;.;T

M_CAP

Benign

0.044

MetaRNN

Benign

0.066

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.90

L;L;L

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.090

Sift

Uncertain

0.0040

D;D;D

Sift4G

Uncertain

0.027

D;D;D

Polyphen

0.0

B;B;B

Vest4

0.32

MutPred

0.13

Gain of glycosylation at P119 (P = 0.0961);Gain of glycosylation at P119 (P = 0.0961);Gain of glycosylation at P119 (P = 0.0961);

MVP

0.10

MPC

1.4

ClinPred

0.18

GERP RS

5.0

Varity_R

0.25

gMVP

0.59

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