3-114886397-C-T

Variant names:

• chr3-114886397-C-T
• rs602164
• NM_001348800.3:c.-417+13907G>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.-417+13907G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.866 in 152,204 control chromosomes in the GnomAD database, including 58,075 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 0.87 (58075 hom., cov: 33)
• Consequence: ZBTB20 NM_001348800.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.627
• Publications: 0 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 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.-417+13907G>A		intron	N/A	NP_001335729.1	Q9HC78-1
	ZBTB20	NM_001348803.3		c.-540+13907G>A		intron	N/A	NP_001335732.1	Q9HC78-1
	ZBTB20	NM_001164343.2		c.-575-12289G>A		intron	N/A	NP_001157815.1	Q9HC78-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB20	ENST00000675478.1	MANE Select	c.-417+13907G>A		intron	N/A	ENSP00000501561.1	Q9HC78-1
	ZBTB20	ENST00000474710.6	TSL:1	c.-597+13907G>A		intron	N/A	ENSP00000419153.1	Q9HC78-1
	ZBTB20	ENST00000357258.8	TSL:1	c.-472+13907G>A		intron	N/A	ENSP00000349803.3	Q9HC78-2

Frequencies

GnomAD3 genomes AF: 0.866 AC: 131725 AN: 152086 Hom.: 58070 Cov.: 33

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.978

Gnomad AMR AF: 0.924

Gnomad ASJ AF: 0.860

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.963

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.938

Gnomad OTH AF: 0.880

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

GnomAD4 genome AF: 0.866 AC: 131773 AN: 152204 Hom.: 58075 Cov.: 33 AF XY: 0.869 AC XY: 64669 AN XY: 74446

African (AFR) AF: 0.684 AC: 28349 AN: 41448

American (AMR) AF: 0.924 AC: 14139 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.860 AC: 2987 AN: 3472

East Asian (EAS) AF: 0.995 AC: 5165 AN: 5192

South Asian (SAS) AF: 0.852 AC: 4106 AN: 4822

European-Finnish (FIN) AF: 0.963 AC: 10226 AN: 10618

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.938 AC: 63805 AN: 68032

Other (OTH) AF: 0.876 AC: 1852 AN: 2114

Alfa AF: 0.895 Hom.: 7206

Bravo AF: 0.857

Asia WGS AF: 0.852 AC: 2964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.66
DANN	Benign	0.71
PhyloP100		-0.63
Mutation Taster		=100/0	polymorphism (auto)

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: rs602164; hg19: chr3-114605244;