Genetic Variant NM_032367.4:c.193C>A (chr5-77077686-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_032367.4(ZBED3):c.193C>A(p.His65Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000033 in 1,211,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000033 ( 0 hom. )

Consequence

ZBED3
NM_032367.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.02

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: 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=0.08964437).

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.193C>A	p.His65Asn	missense	Exon 3 of 3	NP_115743.1	Q96IU2
	ZBED3	NM_001329564.2		c.193C>A	p.His65Asn	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.193C>A	p.His65Asn	missense	Exon 3 of 3	ENSP00000255198.2	Q96IU2
ENSG00000285000	ENST00000646704.1		n.1809+15884G>T		intron	N/A	ENSP00000495089.1	A0A2R8YFF1
ZBED3	ENST00000896398.1		c.193C>A	p.His65Asn	missense	Exon 4 of 4	ENSP00000566457.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000330

AC:

AN:

1211000

Hom.:

Cov.:

AF XY:

0.00000338

AC XY:

AN XY:

592388

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24026

American (AMR)

AF:

0.00

AC:

AN:

12338

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17838

East Asian (EAS)

AF:

0.000148

AC:

AN:

27066

South Asian (SAS)

AF:

0.00

AC:

AN:

53418

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3380

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

995270

Other (OTH)

AF:

0.00

AC:

AN:

49076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.0080

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.50

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.090

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

1.0

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.60

REVEL

Benign

0.018

Sift

Benign

0.18

Sift4G

Benign

0.41

Polyphen

0.26

Vest4

0.17

MutPred

0.32

Loss of helix (P = 0.0558)

MVP

0.014

MPC

1.6

ClinPred

0.11

GERP RS

2.9

Varity_R

0.078

gMVP

0.047

Mutation Taster

=96/4

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over