Variant 11-10853276-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001143667.2(ZBED5):c.1670G>A(p.Arg557His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000029 in 1,551,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

ZBED5
NM_001143667.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.104

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03307447).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBED5	NM_001143667.2 linkuse as main transcript	c.1670G>A	p.Arg557His	missense_variant	3/3	ENST00000413761.7	NP_001137139.1	Q49AG3
ZBED5	NM_021211.4 linkuse as main transcript	c.1670G>A	p.Arg557His	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.1670G>A	p.Arg557His	missense_variant	3/3	1	NM_001143667.2	ENSP00000415939.2	Q49AG3
ZBED5	ENST00000432999.6 linkuse as main transcript	c.1670G>A	p.Arg557His	missense_variant	3/3	1		ENSP00000398106.2	Q49AG3
ZBED5	ENST00000525350.5 linkuse as main transcript	n.75+2868G>A		intron_variant		2
ZBED5	ENST00000533925.5 linkuse as main transcript	n.326+2868G>A		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000392

AC:

AN:

153202

Hom.:

AF XY:

0.00

AC XY:

AN XY:

80998

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000265

Gnomad SAS exome

AF:

0.0000439

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000174

Gnomad OTH exome

AF:

0.000228

GnomAD4 exome

AF:

0.0000279

AC:

AN:

1399298

Hom.:

Cov.:

AF XY:

0.0000188

AC XY:

AN XY:

690150

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000168

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.0000203

Gnomad4 NFE exome

AF:

0.0000269

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000554

Hom.:

Bravo

AF:

0.0000416

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

Feb 28, 2023

The c.1670G>A (p.R557H) alteration is located in exon 3 (coding exon 1) of the ZBED5 gene. This alteration results from a G to A substitution at nucleotide position 1670, causing the arginine (R) at amino acid position 557 to be replaced by a histidine (H). 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

0.099

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.60

CADD

Benign

6.0

DANN

Benign

0.90

DEOGEN2

Benign

0.012

T;T

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.57

.;T

M_CAP

Benign

0.0030

MetaRNN

Benign

0.033

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.34

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.045

Sift

Benign

0.11

T;T

Sift4G

Benign

0.064

T;T

Polyphen

0.16

B;B

Vest4

0.15

MutPred

0.55

Gain of ubiquitination at K562 (P = 0.0577);Gain of ubiquitination at K562 (P = 0.0577);

MVP

0.014

ClinPred

0.040

GERP RS

-0.14

Varity_R

0.035

gMVP

0.51

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