chr10-31461187-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001174096.2(ZEB1):c.209G>A(p.Gly70Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0000021 ( 0 hom. )
Consequence
ZEB1
NM_001174096.2 missense
NM_001174096.2 missense
Scores
1
18
Clinical Significance
Conservation
PhyloP100: 4.46
Genes affected
ZEB1 (HGNC:11642): (zinc finger E-box binding homeobox 1) This gene encodes a zinc finger transcription factor. The encoded protein likely plays a role in transcriptional repression of interleukin 2. Mutations in this gene have been associated with posterior polymorphous corneal dystrophy-3 and late-onset Fuchs endothelial corneal dystrophy. Alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Mar 2010]
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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=0.036073476).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZEB1 | NM_001174096.2 | c.209G>A | p.Gly70Glu | missense_variant | 2/9 | ENST00000424869.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZEB1 | ENST00000424869.6 | c.209G>A | p.Gly70Glu | missense_variant | 2/9 | 5 | NM_001174096.2 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250880Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135580
GnomAD3 exomes
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461150Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 726842
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ExAC
?
AF:
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1
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 14, 2023 | The c.209G>A (p.G70E) alteration is located in exon 2 (coding exon 2) of the ZEB1 gene. This alteration results from a G to A substitution at nucleotide position 209, causing the glycine (G) at amino acid position 70 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;.;.;T;T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T;T;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N;.;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D;D;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T;T
Polyphen
B;.;.;.;.;.;.
Vest4
MutPred
Gain of glycosylation at T66 (P = 0.182);Gain of glycosylation at T66 (P = 0.182);Gain of glycosylation at T66 (P = 0.182);Gain of glycosylation at T66 (P = 0.182);Gain of glycosylation at T66 (P = 0.182);.;.;
MVP
MPC
0.63
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at