Genetic Variant ZBTB4:p.Pro965Ser (chr17-7462089-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001128833.2(ZBTB4):c.2893C>T(p.Pro965Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000405 in 1,604,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P965Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

ZBTB4
NM_001128833.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.02

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2609931).

BS2

High AC in GnomAd4 at 9 AD gene.

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.2893C>T	p.Pro965Ser	missense	Exon 4 of 4	NP_001122305.1	Q9P1Z0
	ZBTB4	NM_020899.4		c.2893C>T	p.Pro965Ser	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.2893C>T	p.Pro965Ser	missense	Exon 4 of 4	ENSP00000369973.4	Q9P1Z0
ZBTB4	ENST00000311403.4	TSL:1	c.2893C>T	p.Pro965Ser	missense	Exon 4 of 4	ENSP00000307858.4	Q9P1Z0
ZBTB4	ENST00000907857.1		c.2893C>T	p.Pro965Ser	missense	Exon 4 of 4	ENSP00000577916.1

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000164

AC:

AN:

243270

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000182

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000385

AC:

AN:

1452674

Hom.:

Cov.:

AF XY:

0.0000471

AC XY:

AN XY:

721888

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33258

American (AMR)

AF:

0.0000229

AC:

AN:

43682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25366

East Asian (EAS)

AF:

0.00

AC:

AN:

39604

South Asian (SAS)

AF:

0.00

AC:

AN:

85038

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53146

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.0000497

AC:

AN:

1106924

Other (OTH)

AF:

0.00

AC:

AN:

59954

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000592

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41424

American (AMR)

AF:

0.000131

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000695

Hom.:

Bravo

AF:

0.0000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000412

AC:

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

Pathogenic

0.72

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

Eigen

Pathogenic

0.68

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.023

MetaRNN

Benign

0.26

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PhyloP100

8.0

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.3

REVEL

Benign

0.24

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.24

MVP

0.20

MPC

1.3

ClinPred

0.47

GERP RS

5.2

Varity_R

0.22

gMVP

0.56

Mutation Taster

=70/30

polymorphism

(source)

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over