rs142830104

Positions:

chr6-109466257-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_014797.3(ZBTB24):c.1688T>C(p.Ile563Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000847 in 1,614,216 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00087 ( 6 hom. )

Consequence

ZBTB24
NM_014797.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 8.51

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01947242).

BP6

Variant 6-109466257-A-G is Benign according to our data. Variant chr6-109466257-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 539538.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000624 (95/152322) while in subpopulation NFE AF= 0.001 (68/68034). AF 95% confidence interval is 0.000808. There are 0 homozygotes in gnomad4. There are 49 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB24	NM_014797.3 linkuse as main transcript	c.1688T>C	p.Ile563Thr	missense_variant	7/7	ENST00000230122.4	NP_055612.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB24	ENST00000230122.4 linkuse as main transcript	c.1688T>C	p.Ile563Thr	missense_variant	7/7	1	NM_014797.3	ENSP00000230122	P1	O43167-1

Frequencies

GnomAD3 genomes

AF:

0.000624

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000999

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000797

AC:

200

AN:

250850

Hom.:

AF XY:

0.000929

AC XY:

126

AN XY:

135560

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00212

Gnomad FIN exome

AF:

0.000647

Gnomad NFE exome

AF:

0.000839

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.000871

AC:

1273

AN:

1461894

Hom.:

Cov.:

AF XY:

0.000956

AC XY:

695

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000402

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00212

Gnomad4 FIN exome

AF:

0.000768

Gnomad4 NFE exome

AF:

0.000846

Gnomad4 OTH exome

AF:

0.000977

GnomAD4 genome

AF:

0.000624

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.000658

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.000999

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00101

Hom.:

Bravo

AF:

0.000623

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000766

AC:

EpiCase

AF:

0.00158

EpiControl

AF:

0.00166

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Immunodeficiency-centromeric instability-facial anomalies syndrome 2

Uncertain:1Benign:1

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 28, 2024	- -
Uncertain significance, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Sep 14, 2023	The ZBTB24 c.1688T>C; p.Ile563Thr variant (rs142830104), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 539538). This variant is found in the general population with an overall allele frequency of 0.08% (222/282,252 alleles, including 2 homozygotes) in the Genome Aggregation Database. Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.233). Due to limited information, the clinical significance of this variant is uncertain at this time. -

ZBTB24-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 23, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

M_CAP

Benign

0.0094

MetaRNN

Benign

0.019

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

MutationTaster

Benign

0.95

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-0.040

REVEL

Benign

0.23

Sift

Uncertain

0.017

Sift4G

Uncertain

0.0060

Polyphen

0.75

Vest4

0.58

MVP

0.34

MPC

0.56

ClinPred

0.051

GERP RS

6.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.069

gMVP

0.38

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