Variant chr17-7462544-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000380599.9(ZBTB4):c.2438A>G(p.Asp813Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000792 in 1,613,764 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00081 ( 2 hom. )

Consequence

ZBTB4
ENST00000380599.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.83

Variant links:

Genes affected

ZBTB4 (HGNC:23847): (zinc finger and BTB domain containing 4) Enables several functions, including DNA-binding transcription repressor activity, RNA polymerase II-specific; methyl-CpNpG binding activity; and sequence-specific DNA binding activity. Involved in cellular response to DNA damage stimulus and negative regulation of transcription by RNA polymerase II. Located in cytosol and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB4 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=0.013600677).

BS2

High AC in GnomAd4 at 92 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB4	NM_001128833.2 linkuse as main transcript	c.2438A>G	p.Asp813Gly	missense_variant	4/4	ENST00000380599.9	NP_001122305.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB4	ENST00000380599.9 linkuse as main transcript	c.2438A>G	p.Asp813Gly	missense_variant	4/4	1	NM_001128833.2	ENSP00000369973	P1
ZBTB4	ENST00000311403.4 linkuse as main transcript	c.2438A>G	p.Asp813Gly	missense_variant	4/4	1		ENSP00000307858	P1

Frequencies

GnomAD3 genomes

AF:

0.000605

AC:

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00549

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.000659

AC:

165

AN:

250218

Hom.:

AF XY:

0.000686

AC XY:

AN XY:

135580

show subpopulations

Gnomad AFR exome

AF:

0.0000623

Gnomad AMR exome

AF:

0.000550

Gnomad ASJ exome

AF:

0.0000997

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000359

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00112

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.000811

AC:

1186

AN:

1461572

Hom.:

Cov.:

AF XY:

0.000821

AC XY:

597

AN XY:

727104

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000492

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000406

Gnomad4 FIN exome

AF:

0.0000752

Gnomad4 NFE exome

AF:

0.000955

Gnomad4 OTH exome

AF:

0.000679

GnomAD4 genome

AF:

0.000605

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.000632

AC XY:

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000824

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.000941

Hom.:

Bravo

AF:

0.000676

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000642

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00218

EpiControl

AF:

0.00148

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 01, 2023

The c.2438A>G (p.D813G) alteration is located in exon 4 (coding exon 2) of the ZBTB4 gene. This alteration results from a A to G substitution at nucleotide position 2438, causing the aspartic acid (D) at amino acid position 813 to be replaced by a glycine (G). 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

0.092

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.016

T;T

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.047

M_CAP

Benign

0.0065

MetaRNN

Benign

0.014

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.34

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.91

N;N

REVEL

Benign

0.017

Sift

Benign

0.15

T;T

Sift4G

Benign

0.13

T;T

Polyphen

0.0

B;B

Vest4

0.13

MVP

0.043

MPC

0.58

ClinPred

0.010

GERP RS

2.9

Varity_R

0.063

gMVP

0.37

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