10-31521854-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PM5BP4

The NM_001174096.2(ZEB1):​c.2522A>G​(p.Gln841Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q841P) has been classified as Pathogenic.

Frequency

Genomes: not found (cov: 32)

Consequence

ZEB1
NM_001174096.2 missense

Scores

2
7
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.01
Variant links:
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 Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr10-31521854-A-C is described in Lovd as [Pathogenic].
BP4
Computational evidence support a benign effect (MetaRNN=0.3998798).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZEB1NM_001174096.2 linkuse as main transcriptc.2522A>G p.Gln841Arg missense_variant 7/9 ENST00000424869.6 NP_001167567.1 P37275-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZEB1ENST00000424869.6 linkuse as main transcriptc.2522A>G p.Gln841Arg missense_variant 7/95 NM_001174096.2 ENSP00000415961.2 P37275-2F6TDF5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250532
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135368
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.34
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
0.030
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.25
T;.;.;.;.
Eigen
Pathogenic
0.71
Eigen_PC
Pathogenic
0.72
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.79
T;T;T;T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.40
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.8
L;.;.;.;.
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-1.5
N;N;N;N;N
REVEL
Uncertain
0.33
Sift
Benign
0.041
D;D;D;D;D
Sift4G
Uncertain
0.060
T;T;T;T;T
Polyphen
0.99
D;.;.;.;.
Vest4
0.37
MutPred
0.52
Gain of solvent accessibility (P = 0.0128);.;.;.;.;
MVP
0.65
MPC
0.13
ClinPred
0.43
T
GERP RS
5.7
Varity_R
0.17
gMVP
0.52

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs118020901; hg19: chr10-31810782; API