6-109481448-C-T

Variant names:

• chr6-109481448-C-T
• rs2227263
• NM_014797.3:c.579G>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_014797.3(ZBTB24):​c.579G>A​(p.Gln193Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0223 in 1,614,168 control chromosomes in the GnomAD database, including 1,312 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (130 hom., cov: 32)
  • Exomes 𝑓: 0.022 (1182 hom.)
• Consequence: ZBTB24 NM_014797.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00400
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 6-109481448-C-T is Benign according to our data. Variant chr6-109481448-C-T is described in ClinVar as Benign. ClinVar VariationId is 472203.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.004 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0999 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.579G>A	p.Gln193Gln	synonymous	Exon 2 of 7	NP_055612.2
	ZBTB24	NM_001164313.2		c.579G>A	p.Gln193Gln	synonymous	Exon 2 of 2	NP_001157785.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB24	ENST00000230122.4	TSL:1 MANE Select	c.579G>A	p.Gln193Gln	synonymous	Exon 2 of 7	ENSP00000230122.4
	ZBTB24	ENST00000698516.1		c.579G>A	p.Gln193Gln	synonymous	Exon 2 of 7	ENSP00000513766.1
	ZBTB24	ENST00000698513.1		c.579G>A	p.Gln193Gln	synonymous	Exon 2 of 6	ENSP00000513763.1

Frequencies

GnomAD3 genomes AF: 0.0224 AC: 3406 AN: 152166 Hom.: 130 Cov.: 32

Gnomad AFR AF: 0.00485

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.0194

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0178

Gnomad OTH AF: 0.0273

GnomAD2 exomes AF: 0.0395 AC: 9934 AN: 251438 AF XY: 0.0323

Gnomad AFR exome AF: 0.00314

Gnomad AMR exome AF: 0.203

Gnomad ASJ exome AF: 0.0118

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0156

Gnomad NFE exome AF: 0.0188

Gnomad OTH exome AF: 0.0358

GnomAD4 exome AF: 0.0223 AC: 32665 AN: 1461884 Hom.: 1182 Cov.: 31 AF XY: 0.0209 AC XY: 15214 AN XY: 727240

African (AFR) AF: 0.00343 AC: 115 AN: 33480

American (AMR) AF: 0.191 AC: 8529 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0113 AC: 296 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00168 AC: 145 AN: 86258

European-Finnish (FIN) AF: 0.0180 AC: 959 AN: 53410

Middle Eastern (MID) AF: 0.00312 AC: 18 AN: 5768

European-Non Finnish (NFE) AF: 0.0192 AC: 21310 AN: 1112012

Other (OTH) AF: 0.0214 AC: 1293 AN: 60396

GnomAD4 genome AF: 0.0224 AC: 3408 AN: 152284 Hom.: 130 Cov.: 32 AF XY: 0.0232 AC XY: 1725 AN XY: 74466

African (AFR) AF: 0.00484 AC: 201 AN: 41548

American (AMR) AF: 0.104 AC: 1593 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 37 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4832

European-Finnish (FIN) AF: 0.0194 AC: 206 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0178 AC: 1208 AN: 68030

Other (OTH) AF: 0.0270 AC: 57 AN: 2112

Alfa AF: 0.0252 Hom.: 156

Bravo AF: 0.0309

Asia WGS AF: 0.00722 AC: 25 AN: 3478

EpiCase AF: 0.0187

EpiControl AF: 0.0148

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	5.6
DANN	Benign	0.44
PhyloP100		-0.0040
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2227263; hg19: chr6-109802651;