rs2232448

chr6-109466393-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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. 14/20 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.156

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBTB24	NM_014797.3	c.1552G>A	p.Ala518Thr	missense_variant	7/7	ENST00000230122.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBTB24	ENST00000230122.4	c.1552G>A	p.Ala518Thr	missense_variant	7/7	1	NM_014797.3	P1

Frequencies

GnomAD3 genomes AF: 0.0776 AC: 11796 AN: 152104 Hom.: 1227 Cov.: 32

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

GnomAD3 exomes AF: 0.0294 AC: 7388 AN: 251468 Hom.: 526 AF XY: 0.0256 AC XY: 3481 AN XY: 135902

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 SAS exome AF: 0.0192

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.: 33 AF XY: 0.0206 AC XY: 14987 AN XY: 727246

Gnomad4 AFR exome AF: 0.247

Gnomad4 AMR exome AF: 0.0187

Gnomad4 ASJ exome AF: 0.0115

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0193

Gnomad4 FIN exome AF: 0.00786

Gnomad4 NFE exome AF: 0.0161

Gnomad4 OTH exome AF: 0.0286

GnomAD4 genome AF: 0.0776 AC: 11819 AN: 152222 Hom.: 1229 Cov.: 32 AF XY: 0.0742 AC XY: 5525 AN XY: 74442

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.0346

Gnomad4 ASJ AF: 0.00835

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0160

Gnomad4 FIN AF: 0.00631

Gnomad4 NFE AF: 0.0160

Gnomad4 OTH AF: 0.0536

Alfa AF: 0.0286 Hom.: 451

Bravo AF: 0.0866

TwinsUK AF: 0.0175 AC: 65

ALSPAC AF: 0.0135 AC: 52

ESP6500AA AF: 0.236 AC: 1041

ESP6500EA AF: 0.0150 AC: 129

ExAC AF: 0.0342 AC: 4149

Asia WGS AF: 0.0230 AC: 78 AN: 3478

EpiCase AF: 0.0161

EpiControl AF: 0.0135

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Immunodeficiency-centromeric instability-facial anomalies syndrome 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.86
Cadd	Benign	5.2
Dann	Benign	0.75
DEOGEN2	Benign	0.0056	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.42	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.31	N
REVEL	Benign	0.13
Sift	Benign	0.44	T
Sift4G	Benign	0.41	T
Polyphen		0.0	B
Vest4		0.016
MPC		0.16
ClinPred		0.0012	T
GERP RS		0.90
Varity_R		0.022
gMVP		0.23

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

Other links and lift over

dbSNP: rs2232448; hg19: chr6-109787596;