Genetic Variant ZBED5:p.Glu536Asp (chr11-10853338-T-A) – 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_001143667.2(ZBED5):c.1608A>T(p.Glu536Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000516 in 1,551,506 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

ZBED5
NM_001143667.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.842

Publications

0 publications found

Variant links:

Genes affected

ZBED5 (HGNC:30803): (zinc finger BED-type containing 5) This gene is unusual in that its coding sequence is mostly derived from Charlie-like DNA transposon; however, it does not appear to be an active DNA transposon as it is not flanked by terminal inverted repeats. The encoded protein is conserved among the mammalian Laurasiatheria branch. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jan 2009]

ZBED5 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=0.1400443).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143667.2. 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
	ZBED5	NM_001143667.2	MANE Select	c.1608A>T	p.Glu536Asp	missense	Exon 3 of 3	NP_001137139.1	Q49AG3
	ZBED5	NM_021211.4		c.1608A>T	p.Glu536Asp	missense	Exon 3 of 3	NP_067034.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZBED5	ENST00000413761.7	TSL:1 MANE Select	c.1608A>T	p.Glu536Asp	missense	Exon 3 of 3	ENSP00000415939.2	Q49AG3
ZBED5	ENST00000432999.6	TSL:1	c.1608A>T	p.Glu536Asp	missense	Exon 3 of 3	ENSP00000398106.2	Q49AG3
ZBED5	ENST00000876894.1		c.1608A>T	p.Glu536Asp	missense	Exon 2 of 2	ENSP00000546953.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000196

AC:

AN:

152838

AF XY:

0.0000247

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000121

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000500

AC:

AN:

1399328

Hom.:

Cov.:

AF XY:

0.00000580

AC XY:

AN XY:

690164

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31596

American (AMR)

AF:

0.000196

AC:

AN:

35702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25176

East Asian (EAS)

AF:

0.00

AC:

AN:

35736

South Asian (SAS)

AF:

0.00

AC:

AN:

79228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49266

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078928

Other (OTH)

AF:

0.00

AC:

AN:

57998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

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

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41456

American (AMR)

AF:

0.0000655

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5204

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.0000264

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

0.23

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0082

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.081

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.52

M_CAP

Benign

0.0041

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.40

PhyloP100

0.84

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.5

REVEL

Benign

0.039

Sift

Benign

0.21

Sift4G

Benign

0.42

Polyphen

0.53

Vest4

0.20

MutPred

0.58

Loss of helix (P = 0.0626)

MVP

0.088

ClinPred

0.14

GERP RS

2.8

Varity_R

0.15

gMVP

0.46

Mutation Taster

=98/2

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