rs778110573

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBS1_Supporting

The NM_014797.3(ZBTB24):c.1666G>A(p.Val556Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000737 in 1,614,066 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 (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

ZBTB24
NM_014797.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.42

Publications

3 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: Likely_benign. The variant received -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15964004).

BS1

Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.0000752 (110/1461892) while in subpopulation SAS AF = 0.000394 (34/86258). AF 95% confidence interval is 0.00029. There are 0 homozygotes in GnomAdExome4. There are 68 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB24	NM_014797.3 link	c.1666G>A	p.Val556Ile	missense_variant	Exon 7 of 7	ENST00000230122.4	NP_055612.2	O43167-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB24	ENST00000230122.4 link	c.1666G>A	p.Val556Ile	missense_variant	Exon 7 of 7	1	NM_014797.3	ENSP00000230122.4		O43167-1

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000136

AC:

AN:

250834

AF XY:

0.000170

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000508

Gnomad NFE exome

AF:

0.0000530

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000752

AC:

110

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0000935

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000394

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000599

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000369

AC:

AN:

1112012

Other (OTH)

AF:

0.0000497

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

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:

0.0000591

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41428

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000659

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

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:

0.0000767

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.000157

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Immunodeficiency-centromeric instability-facial anomalies syndrome 2

Uncertain:1

Sep 01, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.36

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.023

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PhyloP100

7.4

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.28

REVEL

Benign

0.22

Sift

Uncertain

0.028

Sift4G

Uncertain

0.0090

Polyphen

1.0

Vest4

0.42

MVP

0.25

MPC

0.62

ClinPred

0.26

GERP RS

6.1

PromoterAI

-0.052

Neutral

(source)

Varity_R

0.11

gMVP

0.20

Mutation Taster

=92/8

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over