Variant chr7-122304044-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001024613.4(FEZF1):c.394G>A(p.Ala132Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000711 in 1,406,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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: 7.1e-7 ( 0 hom. )

Consequence

FEZF1
NM_001024613.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.19

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0985173).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FEZF1	NM_001024613.4 linkuse as main transcript	c.394G>A	p.Ala132Thr	missense_variant	1/4	ENST00000442488.7	NP_001019784.2
FEZF1-AS1	NR_036484.1 linkuse as main transcript	n.387C>T		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FEZF1	ENST00000442488.7 linkuse as main transcript	c.394G>A	p.Ala132Thr	missense_variant	1/4	1	NM_001024613.4	ENSP00000411145	P2	A0PJY2-1
FEZF1	ENST00000427185.2 linkuse as main transcript	c.394G>A	p.Ala132Thr	missense_variant	1/5	1		ENSP00000392727	A2	A0PJY2-2
FEZF1-AS1	ENST00000428449.5 linkuse as main transcript	n.387C>T		non_coding_transcript_exon_variant	1/7	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.11e-7

AC:

AN:

1406274

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

695526

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

9.21e-7

Gnomad4 OTH exome

AF:

0.00

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

Jun 26, 2023

The c.394G>A (p.A132T) alteration is located in exon 1 (coding exon 1) of the FEZF1 gene. This alteration results from a G to A substitution at nucleotide position 394, causing the alanine (A) at amino acid position 132 to be replaced by a threonine (T). 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

0.15

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.093

T;.

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.26

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.79

T;D

M_CAP

Benign

0.0072

MetaRNN

Benign

0.099

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

0.97

N;N;N

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.40

N;N

REVEL

Benign

0.059

Sift

Benign

0.035

D;T

Sift4G

Benign

0.47

T;T

Polyphen

0.0010

B;B

Vest4

0.081

MutPred

0.43

Gain of phosphorylation at A132 (P = 0.1215);Gain of phosphorylation at A132 (P = 0.1215);

MVP

0.17

ClinPred

0.56

GERP RS

3.8

Varity_R

0.058

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over