Variant 11-10853384-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.1562A>T(p.Glu521Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000142 in 1,551,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

ZBED5
NM_001143667.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.51

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=0.120138794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBED5	NM_001143667.2 linkuse as main transcript	c.1562A>T	p.Glu521Val	missense_variant	3/3	ENST00000413761.7	NP_001137139.1	Q49AG3
ZBED5	NM_021211.4 linkuse as main transcript	c.1562A>T	p.Glu521Val	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.1562A>T	p.Glu521Val	missense_variant	3/3	1	NM_001143667.2	ENSP00000415939.2	Q49AG3
ZBED5	ENST00000432999.6 linkuse as main transcript	c.1562A>T	p.Glu521Val	missense_variant	3/3	1		ENSP00000398106.2	Q49AG3
ZBED5	ENST00000525350.5 linkuse as main transcript	n.75+2760A>T		intron_variant		2
ZBED5	ENST00000533925.5 linkuse as main transcript	n.326+2760A>T		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152216

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:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000792

AC:

AN:

151498

Hom.:

AF XY:

0.0000373

AC XY:

AN XY:

80438

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000408

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:

0.000176

Gnomad OTH exome

AF:

0.000232

GnomAD4 exome

AF:

0.000149

AC:

208

AN:

1398768

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

103

AN XY:

689844

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000562

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:

0.000184

Gnomad4 OTH exome

AF:

0.000121

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000112

Hom.:

Bravo

AF:

0.0000529

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000455

AC:

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

Jul 05, 2023

The c.1562A>T (p.E521V) 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 1562, causing the glutamic acid (E) at amino acid position 521 to be replaced by a valine (V). 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

0.17

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.061

T;T

Eigen

Benign

-0.043

Eigen_PC

Benign

0.051

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.52

.;T

M_CAP

Benign

0.0058

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.4

L;L

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-2.9

D;D

REVEL

Benign

0.12

Sift

Benign

0.041

D;D

Sift4G

Benign

0.23

T;T

Polyphen

0.39

B;B

Vest4

0.40

MutPred

0.55

Loss of disorder (P = 0.0272);Loss of disorder (P = 0.0272);

MVP

0.33

ClinPred

0.13

GERP RS

4.0

Varity_R

0.23

gMVP

0.48

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