chr6-109466393-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_014797.3(ZBTB24):c.1552G>A(p.Ala518Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0267 in 1,614,114 control chromosomes in the GnomAD database, including 2,559 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 Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A518G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.078 ( 1229 hom., cov: 32)

Exomes 𝑓: 0.021 ( 1330 hom. )

Consequence

ZBTB24
NM_014797.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.156

Publications

13 publications found

Variant links:

Genes affected

ZBTB24 (HGNC:21143): (zinc finger and BTB domain containing 24) Predicted to enable DNA-binding transcription factor activity and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within hematopoietic progenitor cell differentiation. Predicted to be located in nucleus. Implicated in immunodeficiency-centromeric instability-facial anomalies syndrome 2. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB24 Gene-Disease associations (from GenCC):

immunodeficiency-centromeric instability-facial anomalies syndrome 2
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
immunodeficiency-centromeric instability-facial anomalies syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ZBTB24 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028230548).

BP6

Variant 6-109466393-C-T is Benign according to our data. Variant chr6-109466393-C-T is described in ClinVar as Benign. ClinVar VariationId is 472200.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014797.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB24	NM_014797.3	MANE Select	c.1552G>A	p.Ala518Thr	missense	Exon 7 of 7	NP_055612.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ZBTB24	ENST00000230122.4	TSL:1 MANE Select	c.1552G>A	p.Ala518Thr	missense	Exon 7 of 7	ENSP00000230122.4
ZBTB24	ENST00000698516.1		c.1552G>A	p.Ala518Thr	missense	Exon 7 of 7	ENSP00000513766.1
ZBTB24	ENST00000698513.1		c.1384G>A	p.Ala462Thr	missense	Exon 6 of 6	ENSP00000513763.1

Frequencies

GnomAD3 genomes

AF:

0.0776

AC:

11796

AN:

152104

Hom.:

1227

Cov.:

show subpopulations

Gnomad AFR

AF:

0.238

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.0346

Gnomad ASJ

AF:

0.00835

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.00631

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0160

Gnomad OTH

AF:

0.0537

GnomAD2 exomes

AF:

0.0294

AC:

7388

AN:

251468

AF XY:

0.0256

show subpopulations

Gnomad AFR exome

AF:

0.244

Gnomad AMR exome

AF:

0.0182

Gnomad ASJ exome

AF:

0.0112

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00693

Gnomad NFE exome

AF:

0.0160

Gnomad OTH exome

AF:

0.0186

GnomAD4 exome

AF:

0.0214

AC:

31355

AN:

1461892

Hom.:

1330

Cov.:

AF XY:

0.0206

AC XY:

14987

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.247

AC:

8270

AN:

33480

American (AMR)

AF:

0.0187

AC:

835

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0115

AC:

301

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.0193

AC:

1669

AN:

86258

European-Finnish (FIN)

AF:

0.00786

AC:

420

AN:

53420

Middle Eastern (MID)

AF:

0.0352

AC:

203

AN:

5768

European-Non Finnish (NFE)

AF:

0.0161

AC:

17928

AN:

1112010

Other (OTH)

AF:

0.0286

AC:

1726

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

2035

4070

6104

8139

10174

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

810

1620

2430

3240

4050

<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:

0.0776

AC:

11819

AN:

152222

Hom.:

1229

Cov.:

AF XY:

0.0742

AC XY:

5525

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.238

AC:

9864

AN:

41488

American (AMR)

AF:

0.0346

AC:

529

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00835

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5172

South Asian (SAS)

AF:

0.0160

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00631

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0160

AC:

1091

AN:

68030

Other (OTH)

AF:

0.0536

AC:

113

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

474

949

1423

1898

2372

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<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:

0.0392

Hom.:

1128

Bravo

AF:

0.0866

TwinsUK

AF:

0.0175

AC:

ALSPAC

AF:

0.0135

AC:

ESP6500AA

AF:

0.236

AC:

1041

ESP6500EA

AF:

0.0150

AC:

129

ExAC

AF:

0.0342

AC:

4149

Asia WGS

AF:

0.0230

AC:

AN:

3478

EpiCase

AF:

0.0161

EpiControl

AF:

0.0135

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Immunodeficiency-centromeric instability-facial anomalies syndrome 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.2

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.0056

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.18

MetaRNN

Benign

0.0028

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.42

PhyloP100

0.16

PrimateAI

Benign

0.27

PROVEAN

Benign

0.31

REVEL

Benign

0.13

Sift

Benign

0.44

Sift4G

Benign

0.41

Polyphen

0.0

Vest4

0.016

MPC

0.16

ClinPred

0.0012

GERP RS

0.90

PromoterAI

0.013

Neutral

(source)

Varity_R

0.022

gMVP

0.23

Mutation Taster

=98/2

polymorphism (auto)

(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

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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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over