NM_001174096.2:c.271G>T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001174096.2(ZEB1):c.271G>T(p.Gly91Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. G91R) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZEB1
NM_001174096.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.75

Publications

0 publications found

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]

ZEB1 Gene-Disease associations (from GenCC):

posterior polymorphous corneal dystrophy 3
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
Fuchs' endothelial dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
posterior polymorphous corneal dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
corneal dystrophy, Fuchs endothelial, 6
Inheritance: AD Classification: LIMITED Submitted by: G2P

ZEB1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19885322).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001174096.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZEB1	NM_001174096.2	MANE Select	c.271G>T	p.Gly91Trp	missense	Exon 3 of 9	NP_001167567.1	P37275-2
ZEB1	NM_001323638.2		c.-387G>T		5_prime_UTR_premature_start_codon_gain	Exon 7 of 13	NP_001310567.1
ZEB1	NM_001323641.2		c.-387G>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 9	NP_001310570.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZEB1	ENST00000424869.6	TSL:5 MANE Select	c.271G>T	p.Gly91Trp	missense	Exon 3 of 9	ENSP00000415961.2	P37275-2
ZEB1	ENST00000320985.14	TSL:1	c.268G>T	p.Gly90Trp	missense	Exon 3 of 9	ENSP00000319248.9	P37275-1
ZEB1	ENST00000558440.5	TSL:1	c.260-14886G>T		intron	N/A	ENSP00000453970.1	H0YND9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460762

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726670

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33434

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26090

East Asian (EAS)

AF:

0.00

AC:

AN:

39656

South Asian (SAS)

AF:

0.00

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111130

Other (OTH)

AF:

0.0000166

AC:

AN:

60332

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.053

BayesDel_noAF

Benign

-0.16

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.22

Eigen

Benign

0.11

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.064

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.65

MutationAssessor

Benign

1.5

PhyloP100

1.7

PrimateAI

Benign

0.37

PROVEAN

Benign

0.010

REVEL

Uncertain

0.37

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0090

Polyphen

0.93

Vest4

0.36

MutPred

0.16

Gain of methylation at K88 (P = 0.167)

MVP

0.66

MPC

1.1

ClinPred

0.61

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.049

gMVP

0.092

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over