chr10-31520308-C-G

Variant names:

• chr10-31520308-C-G
• rs1057518956
• NM_001174096.2:c.976C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001174096.2(ZEB1):​c.976C>G​(p.Arg326Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZEB1 NM_001174096.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.55
• Publications: 10 publications found

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: G2P, Labcorp Genetics (formerly Invitae)
• 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

ACMG classification

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=0.23124218).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZEB1	NM_001174096.2	MANE Select	c.976C>G	p.Arg326Gly	missense	Exon 7 of 9	NP_001167567.1
	ZEB1	NM_030751.6		c.973C>G	p.Arg325Gly	missense	Exon 7 of 9	NP_110378.3
	ZEB1	NM_001323676.2		c.934C>G	p.Arg312Gly	missense	Exon 7 of 9	NP_001310605.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZEB1	ENST00000424869.6	TSL:5 MANE Select	c.976C>G	p.Arg326Gly	missense	Exon 7 of 9	ENSP00000415961.2
	ZEB1	ENST00000320985.14	TSL:1	c.973C>G	p.Arg325Gly	missense	Exon 7 of 9	ENSP00000319248.9
	ZEB1	ENST00000558440.5	TSL:1	c.751C>G	p.Arg251Gly	missense	Exon 5 of 5	ENSP00000453970.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.6
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.15
Sift	Benign	0.037	D
Sift4G	Benign	0.49	T
Polyphen		0.86	P
Vest4		0.70
MutPred		0.26		Gain of loop (P = 0.0166)
MVP		0.50
MPC		0.32
ClinPred		0.76	D
GERP RS		2.3
Varity_R		0.22
gMVP		0.56
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs1057518956; hg19: chr10-31809236;