Genetic Variant ZBTB4:p.Val1004Ile (chr17-7461972-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001128833.2(ZBTB4):c.3010G>A(p.Val1004Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZBTB4
NM_001128833.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.936

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.034396917).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128833.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB4	NM_001128833.2	MANE Select	c.3010G>A	p.Val1004Ile	missense	Exon 4 of 4	NP_001122305.1	Q9P1Z0
	ZBTB4	NM_020899.4		c.3010G>A	p.Val1004Ile	missense	Exon 4 of 4	NP_065950.2	Q9P1Z0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZBTB4	ENST00000380599.9	TSL:1 MANE Select	c.3010G>A	p.Val1004Ile	missense	Exon 4 of 4	ENSP00000369973.4	Q9P1Z0
ZBTB4	ENST00000311403.4	TSL:1	c.3010G>A	p.Val1004Ile	missense	Exon 4 of 4	ENSP00000307858.4	Q9P1Z0
ZBTB4	ENST00000907857.1		c.3010G>A	p.Val1004Ile	missense	Exon 4 of 4	ENSP00000577916.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1428722

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

707338

African (AFR)

AF:

0.00

AC:

AN:

32664

American (AMR)

AF:

0.00

AC:

AN:

41086

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23426

East Asian (EAS)

AF:

0.00

AC:

AN:

39402

South Asian (SAS)

AF:

0.00

AC:

AN:

81074

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52248

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5576

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1094384

Other (OTH)

AF:

0.00

AC:

AN:

58862

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.61

DEOGEN2

Benign

0.0041

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.47

M_CAP

Benign

0.0056

MetaRNN

Benign

0.034

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.55

PhyloP100

0.94

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.090

REVEL

Benign

0.024

Sift

Benign

0.26

Sift4G

Benign

0.48

Polyphen

0.0

Vest4

0.032

MutPred

0.20

Gain of sheet (P = 0.0344)

MVP

0.043

MPC

0.35

ClinPred

0.064

GERP RS

0.10

Varity_R

0.020

gMVP

0.055

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over