6-109462738-A-G

Variant names:

• chr6-109462738-A-G
• rs1046943
• ENST00000230122:c.*3113T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014797.3(ZBTB24):​c.*3113T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 152,006 control chromosomes in the GnomAD database, including 21,448 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.52 (21447 hom., cov: 32)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: ZBTB24 NM_014797.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.563

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]

MICAL1 (HGNC:20619): (microtubule associated monooxygenase, calponin and LIM domain containing 1) This gene encodes an enzyme that oxidizes methionine residues on actin, thereby promoting depolymerization of actin filaments. This protein interacts with and regulates signalling by NEDD9/CAS-L (neural precursor cell expressed, developmentally down-regulated 9). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB24	NM_014797.3	c.*3113T>C		3_prime_UTR_variant	Exon 7 of 7	ENST00000230122.4	NP_055612.2
MICAL1	NM_001286613.2	c.14+2926T>C		intron_variant	Intron 1 of 24		NP_001273542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB24	ENST00000230122	c.*3113T>C		3_prime_UTR_variant	Exon 7 of 7	1	NM_014797.3	ENSP00000230122.4

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78609 AN: 151882 Hom.: 21407 Cov.: 32

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.492

GnomAD4 exome AF: 0.500 AC: 3 AN: 6 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 3 AN XY: 6

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.518 AC: 78712 AN: 152000 Hom.: 21447 Cov.: 32 AF XY: 0.519 AC XY: 38593 AN XY: 74290

Gnomad4 AFR AF: 0.705

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.516

Gnomad4 SAS AF: 0.534

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.415

Gnomad4 OTH AF: 0.492

Alfa AF: 0.437 Hom.: 21257

Bravo AF: 0.526

Asia WGS AF: 0.549 AC: 1908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.9
DANN	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1046943; hg19: chr6-109783941;