Variant 3-62372201-G-A 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.668C>T(p.Ala223Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000193 in 1,576,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.00020 ( 0 hom. )

Consequence

FEZF2
NM_018008.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.97

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=0.037337184).

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.668C>T	p.Ala223Val	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.668C>T	p.Ala223Val	missense_variant	2/5	1	NM_018008.4	ENSP00000283268.3	Q8TBJ5-1
FEZF2	ENST00000475839.1 linkuse as main transcript	c.668C>T	p.Ala223Val	missense_variant	1/4	1		ENSP00000418804.1	Q8TBJ5-1
FEZF2	ENST00000486811.5 linkuse as main transcript	c.668C>T	p.Ala223Val	missense_variant	3/6	5		ENSP00000418589.1	Q8TBJ5-1

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000250

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000240

AC:

AN:

183596

Hom.:

AF XY:

0.000222

AC XY:

AN XY:

99194

show subpopulations

Gnomad AFR exome

AF:

0.000403

Gnomad AMR exome

AF:

0.000508

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000239

Gnomad NFE exome

AF:

0.000221

Gnomad OTH exome

AF:

0.00103

GnomAD4 exome

AF:

0.000197

AC:

281

AN:

1424556

Hom.:

Cov.:

AF XY:

0.000193

AC XY:

136

AN XY:

705226

show subpopulations

Gnomad4 AFR exome

AF:

0.0000611

Gnomad4 AMR exome

AF:

0.000489

Gnomad4 ASJ exome

AF:

0.0000394

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000489

Gnomad4 FIN exome

AF:

0.000239

Gnomad4 NFE exome

AF:

0.000216

Gnomad4 OTH exome

AF:

0.000119

GnomAD4 genome

AF:

0.000158

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.000212

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000235

AC:

ExAC

AF:

0.000175

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

May 25, 2022

The c.668C>T (p.A223V) alteration is located in exon 2 (coding exon 1) of the FEZF2 gene. This alteration results from a C to T substitution at nucleotide position 668, causing the alanine (A) at amino acid position 223 to be replaced by a valine (V). 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

0.21

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.20

T;T;T

Eigen

Benign

-0.010

Eigen_PC

Benign

0.061

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.70

.;.;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.037

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.83

L;L;L

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.095

Sift

Benign

0.50

T;T;T

Sift4G

Benign

0.30

T;T;T

Polyphen

0.75

P;P;P

Vest4

0.096

MVP

0.28

MPC

0.52

ClinPred

0.029

GERP RS

5.0

Varity_R

0.17

gMVP

0.26

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