Genetic Variant ZBED3:p.Gly222Val (chr5-77077214-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032367.4(ZBED3):c.665G>T(p.Gly222Val) 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. 14/21 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. G222D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZBED3
NM_032367.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.608

Publications

0 publications found

Variant links:

Genes affected

ZBED3 (HGNC:20711): (zinc finger BED-type containing 3) This gene belongs to a class of genes that arose through hAT DNA transposition and that encode regulatory proteins. This gene is upregulated in lung cancer tissues, where the encoded protein causes an accumulation of beta-catenin and enhanced lung cancer cell invasion. In addition, the encoded protein can be secreted and be involved in resistance to insulin. [provided by RefSeq, Jul 2016]

ZBED3 links:

ENSG00000285000 (HGNC:):

ENSG00000285000 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.058184206).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032367.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBED3	NM_032367.4	MANE Select	c.665G>T	p.Gly222Val	missense	Exon 3 of 3	NP_115743.1	Q96IU2
	ZBED3	NM_001329564.2		c.665G>T	p.Gly222Val	missense	Exon 2 of 2	NP_001316493.1	Q96IU2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZBED3	ENST00000255198.3	TSL:1 MANE Select	c.665G>T	p.Gly222Val	missense	Exon 3 of 3	ENSP00000255198.2	Q96IU2
ENSG00000285000	ENST00000646704.1		n.1809+15412C>A		intron	N/A	ENSP00000495089.1	A0A2R8YFF1
ZBED3	ENST00000896398.1		c.665G>T	p.Gly222Val	missense	Exon 4 of 4	ENSP00000566457.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1348480

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

668350

African (AFR)

AF:

0.00

AC:

AN:

28406

American (AMR)

AF:

0.00

AC:

AN:

31758

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23506

East Asian (EAS)

AF:

0.00

AC:

AN:

30774

South Asian (SAS)

AF:

0.00

AC:

AN:

75442

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34546

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5524

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1062862

Other (OTH)

AF:

0.00

AC:

AN:

55662

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

5.7

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0072

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.39

M_CAP

Benign

0.0025

MetaRNN

Benign

0.058

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

-0.61

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.7

REVEL

Benign

0.067

Sift

Uncertain

0.013

Sift4G

Benign

0.066

Polyphen

0.14

Vest4

0.094

MutPred

0.49

Gain of helix (P = 0.0496)

MVP

0.030

MPC

2.7

ClinPred

0.47

GERP RS

-2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.057

gMVP

0.010

Mutation Taster

=100/0

polymorphism

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over