Variant 17-7462403-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001128833.2(ZBTB4):c.2579T>C(p.Val860Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000185 in 1,461,698 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ZBTB4
NM_001128833.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0500

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04349971).

BS2

High AC in GnomAdExome4 at 27 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB4	NM_001128833.2 linkuse as main transcript	c.2579T>C	p.Val860Ala	missense_variant	4/4	ENST00000380599.9	NP_001122305.1	Q9P1Z0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB4	ENST00000380599.9 linkuse as main transcript	c.2579T>C	p.Val860Ala	missense_variant	4/4	1	NM_001128833.2	ENSP00000369973.4		Q9P1Z0
ZBTB4	ENST00000311403.4 linkuse as main transcript	c.2579T>C	p.Val860Ala	missense_variant	4/4	1		ENSP00000307858.4		Q9P1Z0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250016

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135570

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1461698

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727160

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000201

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:

0.0000153

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

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

May 15, 2024

The c.2579T>C (p.V860A) alteration is located in exon 4 (coding exon 2) of the ZBTB4 gene. This alteration results from a T to C substitution at nucleotide position 2579, causing the valine (V) at amino acid position 860 to be replaced by an alanine (A). 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

0.069

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.73

CADD

Benign

8.2

DANN

Benign

0.90

DEOGEN2

Benign

0.0040

T;T

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.098

M_CAP

Benign

0.0029

MetaRNN

Benign

0.043

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.46

N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.21

N;N

REVEL

Benign

0.025

Sift

Benign

0.20

T;T

Sift4G

Benign

0.81

T;T

Polyphen

0.0010

B;B

Vest4

0.037

MutPred

0.17

Gain of glycosylation at P858 (P = 0.1349);Gain of glycosylation at P858 (P = 0.1349);

MVP

0.043

MPC

0.53

ClinPred

0.058

GERP RS

2.8

Varity_R

0.023

gMVP

0.26

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