3-114553078-C-A

Position:

• chr3-114553078-C-A

Variant summary

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

The NM_001348800.3(ZBTB20):​c.-294-52687G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,068 control chromosomes in the GnomAD database, including 2,217 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 0.16 (2217 hom., cov: 32)
• Consequence: ZBTB20 NM_001348800.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.918

Genes affected

ZBTB20 (HGNC:13503): (zinc finger and BTB domain containing 20) This gene, which was initially designated as dendritic cell-derived BTB/POZ zinc finger (DPZF), belongs to a family of transcription factors with an N-terminal BTB/POZ domain and a C-terminal DNA-bindng zinc finger domain. The BTB/POZ domain is a hydrophobic region of approximately 120 aa which mediates association with other BTB/POZ domain-containing proteins. This gene acts as a transcriptional repressor and plays a role in many processes including neurogenesis, glucose homeostasis, and postnatal growth. Mutations in this gene have been associated with Primrose syndrome as well as the 3q13.31 microdeletion syndrome. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Feb 2017]

ZBTB20 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB20	NM_001348800.3	c.-294-52687G>T		intron_variant		ENST00000675478.1	NP_001335729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB20	ENST00000675478.1	c.-294-52687G>T		intron_variant			NM_001348800.3	ENSP00000501561.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24592 AN: 151950 Hom.: 2214 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.0885

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.142

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.162 AC: 24623 AN: 152068 Hom.: 2217 Cov.: 32 AF XY: 0.160 AC XY: 11886 AN XY: 74334

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.0889

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.144

Alfa AF: 0.145 Hom.: 425

Bravo AF: 0.162

Asia WGS AF: 0.202 AC: 705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.62

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: rs16822925; hg19: chr3-114271925;