7-122302853-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001024613.4(FEZF1):c.1015G>A(p.Ala339Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
FEZF1
NM_001024613.4 missense
NM_001024613.4 missense
Scores
1
8
10
Clinical Significance
Conservation
PhyloP100: 5.99
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.35350025).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FEZF1 | NM_001024613.4 | c.1015G>A | p.Ala339Thr | missense_variant | 3/4 | ENST00000442488.7 | |
FEZF1 | NM_001160264.2 | c.865G>A | p.Ala289Thr | missense_variant | 4/5 | ||
FEZF1 | XM_005250337.4 | c.1015G>A | p.Ala339Thr | missense_variant | 4/5 | ||
FEZF1 | XM_011516202.3 | c.865G>A | p.Ala289Thr | missense_variant | 5/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FEZF1 | ENST00000442488.7 | c.1015G>A | p.Ala339Thr | missense_variant | 3/4 | 1 | NM_001024613.4 | P2 | |
FEZF1 | ENST00000427185.2 | c.865G>A | p.Ala289Thr | missense_variant | 4/5 | 1 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251384Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135862
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461796Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1AN XY: 727202
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
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Cov.:
32
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 | Dec 19, 2023 | The c.1015G>A (p.A339T) alteration is located in exon 3 (coding exon 3) of the FEZF1 gene. This alteration results from a G to A substitution at nucleotide position 1015, causing the alanine (A) at amino acid position 339 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Uncertain
D;T
Polyphen
D;D
Vest4
MutPred
Gain of phosphorylation at A339 (P = 0.0841);.;
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at