Variant 7-122304124-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001024613.4(FEZF1):c.314C>A(p.Ala105Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000277 in 1,444,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

FEZF1
NM_001024613.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.437

Variant links:

Genes affected

FEZF1 (HGNC:22788): (FEZ family zinc finger 1) This gene encodes a transcriptional repressor that belongs to the zinc finger double domain protein family. The encoded protein is thought to play a role in the embryonic migration of gonadotropin-releasing hormone neurons into the brain. Mutations in this gene are associated with hypogonadotropic hypogonadism-22 with anosmia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

FEZF1 links:

FEZF1-AS1 (HGNC:41001): (FEZF1 antisense RNA 1)

FEZF1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.059329093).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FEZF1	NM_001024613.4 link	c.314C>A	p.Ala105Glu	missense_variant	1/4	ENST00000442488.7	NP_001019784.2	A0PJY2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FEZF1	ENST00000442488.7 link	c.314C>A	p.Ala105Glu	missense_variant	1/4	1	NM_001024613.4	ENSP00000411145.2	A0PJY2-1
FEZF1	ENST00000427185.2 link	c.314C>A	p.Ala105Glu	missense_variant	1/5	1		ENSP00000392727.2	A0PJY2-2
FEZF1-AS1	ENST00000428449.5 link	n.467G>T		non_coding_transcript_exon_variant	1/7	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000449

AC:

AN:

222770

Hom.:

AF XY:

0.00

AC XY:

AN XY:

121604

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000595

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000277

AC:

AN:

1444100

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

716286

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000699

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:

0.00

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 08, 2024

The c.314C>A (p.A105E) alteration is located in exon 1 (coding exon 1) of the FEZF1 gene. This alteration results from a C to A substitution at nucleotide position 314, causing the alanine (A) at amino acid position 105 to be replaced by a glutamic acid (E). 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

0.25

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.15

T;.

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.0081

MetaRNN

Benign

0.059

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.041

Sift

Benign

0.055

T;T

Sift4G

Uncertain

0.042

D;T

Polyphen

0.042

B;B

Vest4

0.20

MutPred

0.18

Gain of solvent accessibility (P = 0.08);Gain of solvent accessibility (P = 0.08);

MVP

0.092

ClinPred

0.080

GERP RS

2.6

Varity_R

0.16

gMVP

0.23

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