NM_001174096.2:c.119A>G

Variant names:

• chr10-31461097-A-G
• NM_001174096.2:c.119A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001174096.2(ZEB1):​c.119A>G​(p.His40Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZEB1 NM_001174096.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.58

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZEB1	NM_001174096.2	c.119A>G	p.His40Arg	missense_variant	Exon 2 of 9	ENST00000424869.6	NP_001167567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZEB1	ENST00000424869.6	c.119A>G	p.His40Arg	missense_variant	Exon 2 of 9	5	NM_001174096.2	ENSP00000415961.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Jul 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.119A>G (p.H40R) alteration is located in exon 2 (coding exon 2) of the ZEB1 gene. This alteration results from a A to G substitution at nucleotide position 119, causing the histidine (H) at amino acid position 40 to be replaced by an arginine (R). 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	Uncertain	0.46
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T;.;.;T;T;.;T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D;D;D;D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.54	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.17	D
MutationAssessor	Uncertain	2.6	M;M;M;.;.;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-2.2	N;N;N;N;D;N;D
REVEL	Uncertain	0.45
Sift	Benign	0.053	T;D;T;D;T;D;D
Sift4G	Benign	0.40	T;T;T;T;T;T;T
Polyphen		1.0	D;.;.;.;.;.;.
Vest4		0.72
MutPred		0.24		Loss of methylation at K38 (P = 0.0493);Loss of methylation at K38 (P = 0.0493);Loss of methylation at K38 (P = 0.0493);Loss of methylation at K38 (P = 0.0493);Loss of methylation at K38 (P = 0.0493);.;.;
MVP		0.82
MPC		1.5
ClinPred		0.82	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.095
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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.

Other links and lift over

hg19: chr10-31750026;