Variant 1-203798675-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001395895.1(ZBED6):c.1153G>A(p.Val385Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00357 in 1,536,098 control chromosomes in the GnomAD database, including 22 homozygotes. 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 0.0029 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0036 ( 16 hom. )

Consequence

ZBED6
NM_001395895.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.441

Variant links:

Genes affected

ZBED6 (HGNC:33273): (zinc finger BED-type containing 6) The protein encoded by this transposon-derived intronless gene is a transcriptional repressor that binds to the consensus sequence 5'-GCTCGC-3'. The encoded protein has been shown to repress IGF2 transcription. This gene is located within the first intron of the ZC3H11A gene. [provided by RefSeq, Jul 2016]

ZBED6 links:

ZC3H11A (HGNC:29093): (zinc finger CCCH-type containing 11A) Enables RNA binding activity. Involved in poly(A)+ mRNA export from nucleus. Colocalizes with transcription export complex. [provided by Alliance of Genome Resources, Apr 2022]

ZC3H11A links:

ZC3H11A (HGNC:):

ZC3H11A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019299984).

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBED6	NM_001395895.1 linkuse as main transcript	c.1153G>A	p.Val385Ile	missense_variant	1/17	ENST00000550078.3	NP_001382824.1
ZC3H11A	NM_001376342.1 linkuse as main transcript	c.-1588+2881G>A		intron_variant		ENST00000367210.3	NP_001363271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBED6	ENST00000550078.3 linkuse as main transcript	c.1153G>A	p.Val385Ile	missense_variant	1/17	1	NM_001395895.1	ENSP00000447879.1		P86452
ZC3H11A	ENST00000367210.3 linkuse as main transcript	c.-1588+2881G>A		intron_variant		1	NM_001376342.1	ENSP00000356179.1		O75152

Frequencies

GnomAD3 genomes

AF:

0.00289

AC:

440

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.104

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00395

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00171

AC:

230

AN:

134514

Hom.:

AF XY:

0.00165

AC XY:

121

AN XY:

73260

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000695

Gnomad ASJ exome

AF:

0.000362

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00149

Gnomad NFE exome

AF:

0.00375

Gnomad OTH exome

AF:

0.000966

GnomAD4 exome

AF:

0.00364

AC:

5038

AN:

1383820

Hom.:

Cov.:

AF XY:

0.00353

AC XY:

2412

AN XY:

682852

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.000784

Gnomad4 ASJ exome

AF:

0.000477

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.0000631

Gnomad4 FIN exome

AF:

0.00139

Gnomad4 NFE exome

AF:

0.00446

Gnomad4 OTH exome

AF:

0.00190

GnomAD4 genome

AF:

0.00289

AC:

440

AN:

152278

Hom.:

Cov.:

AF XY:

0.00274

AC XY:

204

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000943

Gnomad4 NFE

AF:

0.00395

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00265

Hom.:

Bravo

AF:

0.00317

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00285

AC:

ExAC

AF:

0.000303

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Nov 08, 2022

The c.1153G>A (p.V385I) alteration is located in exon 1 (coding exon 1) of the ZBED6 gene. This alteration results from a G to A substitution at nucleotide position 1153, causing the valine (V) at amino acid position 385 to be replaced by an isoleucine (I). 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

0.075

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.64

CADD

Benign

4.8

DANN

Benign

0.81

DEOGEN2

Benign

0.00035

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.41

M_CAP

Benign

0.0037

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.69

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.12

REVEL

Benign

0.011

Sift

Benign

0.13

Sift4G

Benign

0.17

Vest4

0.039

MVP

0.040

ClinPred

0.029

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.047

gMVP

0.16

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