3-114315251-C-T

Variant names:

• chr3-114315251-C-T
• rs4682534
• NM_001348800.3:c.*23754G>A

Variant summary

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

The NM_001348800.3(ZBTB20):​c.*23754G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.904 in 152,210 control chromosomes in the GnomAD database, including 62,719 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 0.90 (62715 hom., cov: 31)
  • Exomes 𝑓: 0.80 (4 hom.)
• Consequence: ZBTB20 NM_001348800.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 2 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: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Genomics England PanelApp, Ambry Genetics
• diabetes mellitus

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

ENSG00000259976 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348800.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB20	NM_001348800.3	MANE Select	c.*23754G>A		3_prime_UTR	Exon 12 of 12	NP_001335729.1	Q9HC78-1
	ZBTB20	NM_001164342.2		c.*23754G>A		3_prime_UTR	Exon 5 of 5	NP_001157814.1	Q9HC78-1
	ZBTB20	NM_001348803.3		c.*23754G>A		3_prime_UTR	Exon 14 of 14	NP_001335732.1	Q9HC78-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB20	ENST00000675478.1	MANE Select	c.*23754G>A		3_prime_UTR	Exon 12 of 12	ENSP00000501561.1	Q9HC78-1
	ZBTB20	ENST00000357258.8	TSL:1	c.*23754G>A		3_prime_UTR	Exon 10 of 10	ENSP00000349803.3	Q9HC78-2
	ENSG00000259976	ENST00000570269.2	TSL:6	n.14464G>A		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.905 AC: 137586 AN: 152082 Hom.: 62691 Cov.: 31

Gnomad AFR AF: 0.782

Gnomad AMI AF: 0.944

Gnomad AMR AF: 0.951

Gnomad ASJ AF: 0.952

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.929

Gnomad FIN AF: 0.986

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.944

Gnomad OTH AF: 0.918

GnomAD4 exome AF: 0.800 AC: 8 AN: 10 Hom.: 4 Cov.: 0 AF XY: 1.00 AC XY: 4 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.800 AC: 8 AN: 10

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.904 AC: 137659 AN: 152200 Hom.: 62715 Cov.: 31 AF XY: 0.908 AC XY: 67599 AN XY: 74410

African (AFR) AF: 0.782 AC: 32428 AN: 41476

American (AMR) AF: 0.951 AC: 14561 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.952 AC: 3304 AN: 3472

East Asian (EAS) AF: 0.993 AC: 5136 AN: 5170

South Asian (SAS) AF: 0.928 AC: 4477 AN: 4822

European-Finnish (FIN) AF: 0.986 AC: 10460 AN: 10612

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.944 AC: 64214 AN: 68024

Other (OTH) AF: 0.918 AC: 1940 AN: 2114

Alfa AF: 0.933 Hom.: 111806

Bravo AF: 0.896

Asia WGS AF: 0.933 AC: 3243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.45
DANN	Benign	0.82
PhyloP100		-1.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4682534; hg19: chr3-114034098;