Variant 11-10853338-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/19 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

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:

ZBED5 (HGNC:):

ZBED5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1400443).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBED5	NM_001143667.2 linkuse as main transcript	c.1608A>T	p.Glu536Asp	missense_variant	3/3	ENST00000413761.7	NP_001137139.1	Q49AG3
ZBED5	NM_021211.4 linkuse as main transcript	c.1608A>T	p.Glu536Asp	missense_variant	3/3		NP_067034.2	Q49AG3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZBED5	ENST00000413761.7 linkuse as main transcript	c.1608A>T	p.Glu536Asp	missense_variant	3/3	1	NM_001143667.2	ENSP00000415939.2	Q49AG3
ZBED5	ENST00000432999.6 linkuse as main transcript	c.1608A>T	p.Glu536Asp	missense_variant	3/3	1		ENSP00000398106.2	Q49AG3
ZBED5	ENST00000525350.5 linkuse as main transcript	n.75+2806A>T		intron_variant		2
ZBED5	ENST00000533925.5 linkuse as main transcript	n.326+2806A>T		intron_variant		4

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

GnomAD3 exomes

AF:

0.0000196

AC:

AN:

152838

Hom.:

AF XY:

0.0000247

AC XY:

AN XY:

80938

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 SAS 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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000196

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.0000264

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 25, 2023

The c.1608A>T (p.E536D) alteration is located in exon 3 (coding exon 1) of the ZBED5 gene. This alteration results from a A to T substitution at nucleotide position 1608, causing the glutamic acid (E) at amino acid position 536 to be replaced by an aspartic acid (D). 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

Benign

0.23

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0082

T;T

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.081

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.52

.;T

M_CAP

Benign

0.0041

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.40

N;N

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.039

Sift

Benign

0.21

T;T

Sift4G

Benign

0.42

T;T

Polyphen

0.53

P;P

Vest4

0.20

MutPred

0.58

Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);

MVP

0.088

ClinPred

0.14

GERP RS

2.8

Varity_R

0.15

gMVP

0.46

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over