3-114339076-C-T

Position:

chr3-114339076-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP2BP4_ModerateBP6_ModerateBS1BS2

The NM_001348800.3(ZBTB20):c.2155G>A(p.Val719Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000099 in 1,564,964 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 2 hom. )

Consequence

ZBTB20
NM_001348800.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.81

Variant links:

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 links:

ZBTB20 (HGNC:):

ZBTB20 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ZBTB20. . Gene score misZ 4.272 (greater than the threshold 3.09). Trascript score misZ 3.9474 (greater than threshold 3.09). GenCC has associacion of gene with Primrose syndrome, diabetes mellitus.

BP4

Computational evidence support a benign effect (MetaRNN=0.08816722).

BP6

Variant 3-114339076-C-T is Benign according to our data. Variant chr3-114339076-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1991538.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000108 (152/1412762) while in subpopulation SAS AF= 0.00164 (128/77986). AF 95% confidence interval is 0.00141. There are 2 homozygotes in gnomad4_exome. There are 104 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAdExome4 at 152 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB20	NM_001348800.3 linkuse as main transcript	c.2155G>A	p.Val719Ile	missense_variant	12/12	ENST00000675478.1	NP_001335729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB20	ENST00000675478.1 linkuse as main transcript	c.2155G>A	p.Val719Ile	missense_variant	12/12		NM_001348800.3	ENSP00000501561.1		Q9HC78-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000203

AC:

AN:

216660

Hom.:

AF XY:

0.000286

AC XY:

AN XY:

115466

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00185

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000200

Gnomad OTH exome

AF:

0.000194

GnomAD4 exome

AF:

0.000108

AC:

152

AN:

1412762

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

104

AN XY:

696578

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00164

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000166

Gnomad4 OTH exome

AF:

0.000103

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.000239

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.062

.;.;.;.;.;T;.

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.85

.;.;D;.;.;D;.

M_CAP

Benign

0.0086

MetaRNN

Benign

0.088

T;T;T;T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

0.76

.;.;.;.;.;N;.

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.22

N;N;N;N;N;N;N

REVEL

Benign

0.25

Sift

Benign

0.061

T;T;T;T;T;D;T

Sift4G

Pathogenic

0.0

D;D;D;D;D;T;D

Polyphen

1.0

.;.;.;.;.;D;.

Vest4

0.52

MutPred

0.49

.;.;.;.;.;Loss of catalytic residue at V719 (P = 0.0265);.;

MVP

0.41

MPC

2.1

ClinPred

0.11

GERP RS

5.9

Varity_R

0.18

gMVP

0.25

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over