Variant 21-41991067-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001098402.2(ZBTB21):c.3029A>G(p.Asn1010Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000276 in 1,593,172 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

ZBTB21
NM_001098402.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0240

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029776841).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB21	NM_001098402.2 linkuse as main transcript	c.3029A>G	p.Asn1010Ser	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.3029A>G	p.Asn1010Ser	missense_variant	3/3	1	NM_001098402.2	ENSP00000308759.5	Q9ULJ3-1
ZBTB21	ENST00000398499.5 linkuse as main transcript	c.3029A>G	p.Asn1010Ser	missense_variant	4/4	1		ENSP00000381512.1	Q9ULJ3-1
ZBTB21	ENST00000398511.3 linkuse as main transcript	c.3029A>G	p.Asn1010Ser	missense_variant	2/2	1		ENSP00000381523.3	Q9ULJ3-1
ZBTB21	ENST00000398505.7 linkuse as main transcript	c.2426A>G	p.Asn809Ser	missense_variant	4/4	1		ENSP00000381517.3	Q9ULJ3-2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151864

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000426

AC:

AN:

234974

Hom.:

AF XY:

0.00000787

AC XY:

AN XY:

127012

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000926

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000291

AC:

AN:

1441308

Hom.:

Cov.:

AF XY:

0.0000349

AC XY:

AN XY:

715426

show subpopulations

Gnomad4 AFR exome

AF:

0.0000307

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000372

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151864

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74158

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2023

The c.3029A>G (p.N1010S) alteration is located in exon 3 (coding exon 1) of the ZBTB21 gene. This alteration results from a A to G substitution at nucleotide position 3029, causing the asparagine (N) at amino acid position 1010 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.25

DANN

Benign

0.82

DEOGEN2

Benign

0.0077

.;T;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.78

T;.;.;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.030

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

.;N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.33

N;N;N;N

REVEL

Benign

0.015

Sift

Benign

0.27

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0010

B;B;B;B

Vest4

0.022

MutPred

0.33

.;Gain of glycosylation at N1010 (P = 0.0056);Gain of glycosylation at N1010 (P = 0.0056);Gain of glycosylation at N1010 (P = 0.0056);

MVP

0.23

MPC

0.14

ClinPred

0.048

GERP RS

1.1

Varity_R

0.033

gMVP

0.15

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