Variant 1-203798579-A-C 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_001395895.1(ZBED6):c.1057A>C(p.Thr353Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000723 in 1,383,820 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: not found (cov: 33)

Exomes 𝑓: 0.0000072 ( 0 hom. )

Consequence

ZBED6
NM_001395895.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.141

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:

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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=0.041650295).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBED6	NM_001395895.1 linkuse as main transcript	c.1057A>C	p.Thr353Pro	missense_variant	1/17	ENST00000550078.3	NP_001382824.1
ZC3H11A	NM_001376342.1 linkuse as main transcript	c.-1588+2785A>C		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.1057A>C	p.Thr353Pro	missense_variant	1/17	1	NM_001395895.1	ENSP00000447879.1		P86452
ZC3H11A	ENST00000367210.3 linkuse as main transcript	c.-1588+2785A>C		intron_variant		1	NM_001376342.1	ENSP00000356179.1		O75152

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000746

AC:

AN:

134138

Hom.:

AF XY:

0.00

AC XY:

AN XY:

73056

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000191

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000723

AC:

AN:

1383820

Hom.:

Cov.:

AF XY:

0.00000732

AC XY:

AN XY:

682850

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000927

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Jun 17, 2022

The c.1057A>C (p.T353P) alteration is located in exon 1 (coding exon 1) of the ZBED6 gene. This alteration results from a A to C substitution at nucleotide position 1057, causing the threonine (T) at amino acid position 353 to be replaced by a proline (P). 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

0.072

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.37

CADD

Benign

7.0

DANN

Benign

0.77

DEOGEN2

Benign

0.0044

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.35

M_CAP

Benign

0.0067

MetaRNN

Benign

0.042

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.2

REVEL

Benign

0.032

Sift

Benign

0.081

Sift4G

Uncertain

0.023

Vest4

0.071

MutPred

0.21

Loss of helix (P = 0.0304);

MVP

0.030

ClinPred

0.034

GERP RS

-2.9

Varity_R

0.14

gMVP

0.28

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