Variant chr21-41991062-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001098402.2(ZBTB21):c.3034A>G(p.Thr1012Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000486 in 1,591,504 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00061 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00047 ( 3 hom. )

Consequence

ZBTB21
NM_001098402.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.444

Variant links:

Genes affected

ZBTB21 (HGNC:13083): (zinc finger and BTB domain containing 21) Enables several functions, including DNA-binding transcription repressor activity, RNA polymerase II-specific; POZ domain binding activity; and methyl-CpG binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB21 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037144423).

BP6

Variant 21-41991062-T-C is Benign according to our data. Variant chr21-41991062-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2255040.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB21	NM_001098402.2 linkuse as main transcript	c.3034A>G	p.Thr1012Ala	missense_variant	3/3	ENST00000310826.10	NP_001091872.1	Q9ULJ3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZBTB21	ENST00000310826.10 linkuse as main transcript	c.3034A>G	p.Thr1012Ala	missense_variant	3/3	1	NM_001098402.2	ENSP00000308759.5	Q9ULJ3-1
ZBTB21	ENST00000398499.5 linkuse as main transcript	c.3034A>G	p.Thr1012Ala	missense_variant	4/4	1		ENSP00000381512.1	Q9ULJ3-1
ZBTB21	ENST00000398511.3 linkuse as main transcript	c.3034A>G	p.Thr1012Ala	missense_variant	2/2	1		ENSP00000381523.3	Q9ULJ3-1
ZBTB21	ENST00000398505.7 linkuse as main transcript	c.2431A>G	p.Thr811Ala	missense_variant	4/4	1		ENSP00000381517.3	Q9ULJ3-2

Frequencies

GnomAD3 genomes

AF:

0.000619

AC:

AN:

151878

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000721

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000698

AC:

164

AN:

235046

Hom.:

AF XY:

0.000779

AC XY:

AN XY:

127044

show subpopulations

Gnomad AFR exome

AF:

0.0000626

Gnomad AMR exome

AF:

0.000517

Gnomad ASJ exome

AF:

0.00760

Gnomad EAS exome

AF:

0.000112

Gnomad SAS exome

AF:

0.000476

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000546

Gnomad OTH exome

AF:

0.00141

GnomAD4 exome

AF:

0.000473

AC:

681

AN:

1439508

Hom.:

Cov.:

AF XY:

0.000553

AC XY:

395

AN XY:

714178

show subpopulations

Gnomad4 AFR exome

AF:

0.000277

Gnomad4 AMR exome

AF:

0.000542

Gnomad4 ASJ exome

AF:

0.00703

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.000829

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000232

Gnomad4 OTH exome

AF:

0.00145

GnomAD4 genome

AF:

0.000612

AC:

AN:

151996

Hom.:

Cov.:

AF XY:

0.000633

AC XY:

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.0115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000624

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000875

Hom.:

Bravo

AF:

0.000608

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000642

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.30

DANN

Benign

0.73

DEOGEN2

Benign

0.0072

.;T;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0029

LIST_S2

Benign

0.44

T;.;.;T

M_CAP

Benign

0.0035

MetaRNN

Benign

0.0037

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

.;N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.47

N;N;N;N

REVEL

Benign

0.023

Sift

Benign

0.37

T;T;T;T

Sift4G

Benign

0.37

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.032

MVP

0.20

MPC

0.17

ClinPred

0.014

GERP RS

-7.2

Varity_R

0.024

gMVP

0.27

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