Genetic Variant NM_014797.3:c.1701C>T (chr6-109466244-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014797.3(ZBTB24):c.1701C>T(p.Pro567Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0173 in 1,614,176 control chromosomes in the GnomAD database, including 389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 101 hom., cov: 32)

Exomes 𝑓: 0.016 ( 288 hom. )

Consequence

ZBTB24
NM_014797.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.34

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 6-109466244-G-A is Benign according to our data. Variant chr6-109466244-G-A is described in ClinVar as [Benign]. Clinvar id is 472202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.34 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB24	NM_014797.3 link	c.1701C>T	p.Pro567Pro	synonymous_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.1701C>T	p.Pro567Pro	synonymous_variant	Exon 7 of 7	1	NM_014797.3	ENSP00000230122.4		O43167-1

Frequencies

GnomAD3 genomes

AF:

0.0279

AC:

4240

AN:

152168

Hom.:

101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0660

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.0133

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0160

Gnomad FIN

AF:

0.00632

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0153

Gnomad OTH

AF:

0.0220

GnomAD3 exomes

AF:

0.0162

AC:

4062

AN:

250802

Hom.:

AF XY:

0.0160

AC XY:

2164

AN XY:

135528

show subpopulations

Gnomad AFR exome

AF:

0.0677

Gnomad AMR exome

AF:

0.00862

Gnomad ASJ exome

AF:

0.0103

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0189

Gnomad FIN exome

AF:

0.00693

Gnomad NFE exome

AF:

0.0154

Gnomad OTH exome

AF:

0.0132

GnomAD4 exome

AF:

0.0162

AC:

23624

AN:

1461890

Hom.:

288

Cov.:

AF XY:

0.0160

AC XY:

11609

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0649

Gnomad4 AMR exome

AF:

0.00879

Gnomad4 ASJ exome

AF:

0.0110

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0190

Gnomad4 FIN exome

AF:

0.00786

Gnomad4 NFE exome

AF:

0.0157

Gnomad4 OTH exome

AF:

0.0174

GnomAD4 genome

AF:

0.0279

AC:

4242

AN:

152286

Hom.:

101

Cov.:

AF XY:

0.0268

AC XY:

1996

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0659

Gnomad4 AMR

AF:

0.0133

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0153

Gnomad4 FIN

AF:

0.00632

Gnomad4 NFE

AF:

0.0153

Gnomad4 OTH

AF:

0.0223

Alfa

AF:

0.0235

Hom.:

Bravo

AF:

0.0299

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.0152

EpiControl

AF:

0.0125

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Immunodeficiency-centromeric instability-facial anomalies syndrome 2

Benign:2

Oct 23, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.7

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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