rs192918926

chr6-109482013-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS1

The NM_014797.3(ZBTB24):c.14C>T(p.Ser5Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000208 in 1,614,118 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S5S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00047 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (3 hom.)
• Consequence: ZBTB24 NM_014797.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.94

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003807813).
• BP6: Variant 6-109482013-G-A is Benign according to our data. Variant chr6-109482013-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 472199.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000473 (72/152280) while in subpopulation EAS AF= 0.00869 (45/5176). AF 95% confidence interval is 0.00668. There are 0 homozygotes in gnomad4. There are 46 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBTB24	NM_014797.3	c.14C>T	p.Ser5Leu	missense_variant	2/7	ENST00000230122.4
ZBTB24	NM_001164313.2	c.14C>T	p.Ser5Leu	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBTB24	ENST00000230122.4	c.14C>T	p.Ser5Leu	missense_variant	2/7	1	NM_014797.3	P1

Frequencies

GnomAD3 genomes AF: 0.000473 AC: 72 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00867

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000850 AC: 211 AN: 248370 Hom.: 1 AF XY: 0.000778 AC XY: 105 AN XY: 134912

Gnomad AFR exome AF: 0.000194

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0109

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000895

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000180 AC: 263 AN: 1461838 Hom.: 3 Cov.: 31 AF XY: 0.000195 AC XY: 142 AN XY: 727220

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00509

Gnomad4 SAS exome AF: 0.000301

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.000381

GnomAD4 genome AF: 0.000473 AC: 72 AN: 152280 Hom.: 0 Cov.: 32 AF XY: 0.000618 AC XY: 46 AN XY: 74440

Gnomad4 AFR AF: 0.000505

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00869

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000296 Hom.: 0

Bravo AF: 0.000484

ExAC AF: 0.000768 AC: 93

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Aug 16, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

ZBTB24: BP4, BS1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.53
Cadd	Benign	16
Dann	Uncertain	0.98
DEOGEN2	Benign	0.0056	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.0038	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.025
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.037	D
Polyphen		0.23	B
Vest4		0.16
MVP		0.20
MPC		0.16
ClinPred		0.0091	T
GERP RS		3.3
Varity_R		0.057
gMVP		0.21

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: rs192918926; hg19: chr6-109803216;