rs10514757

Variant names:

• chr3-114585306-T-C
• rs10514757
• NM_001348800.3:c.-294-84915A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001348800.3(ZBTB20):​c.-294-84915A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.031 in 152,120 control chromosomes in the GnomAD database, including 120 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 0.031 (120 hom., cov: 32)
• Consequence: ZBTB20 NM_001348800.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.515
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• Primrose syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• diabetes mellitus

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB20	NM_001348800.3	c.-294-84915A>G		intron_variant	Intron 6 of 11	ENST00000675478.1	NP_001335729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB20	ENST00000675478.1	c.-294-84915A>G		intron_variant	Intron 6 of 11		NM_001348800.3	ENSP00000501561.1

Frequencies

GnomAD3 genomes AF: 0.0311 AC: 4720 AN: 152002 Hom.: 121 Cov.: 32

Gnomad AFR AF: 0.00819

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0449

Gnomad ASJ AF: 0.0424

Gnomad EAS AF: 0.0837

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0195

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0337

Gnomad OTH AF: 0.0301

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

GnomAD4 genome AF: 0.0310 AC: 4715 AN: 152120 Hom.: 120 Cov.: 32 AF XY: 0.0324 AC XY: 2413 AN XY: 74384

African (AFR) AF: 0.00817 AC: 339 AN: 41506

American (AMR) AF: 0.0448 AC: 684 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0424 AC: 147 AN: 3466

East Asian (EAS) AF: 0.0839 AC: 433 AN: 5160

South Asian (SAS) AF: 0.113 AC: 545 AN: 4810

European-Finnish (FIN) AF: 0.0195 AC: 207 AN: 10598

Middle Eastern (MID) AF: 0.0240 AC: 7 AN: 292

European-Non Finnish (NFE) AF: 0.0336 AC: 2286 AN: 67980

Other (OTH) AF: 0.0308 AC: 65 AN: 2112

Alfa AF: 0.0349 Hom.: 188

Bravo AF: 0.0289

Asia WGS AF: 0.113 AC: 393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.68
DANN	Benign	0.72
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism

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: rs10514757; hg19: chr3-114304153;