Variant 3-141442474-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001376113.1(ZBTB38):c.86G>A(p.Arg29Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000039 in 1,614,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

ZBTB38
NM_001376113.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.96

Variant links:

Genes affected

ZBTB38 (HGNC:26636): (zinc finger and BTB domain containing 38) The protein encoded by this gene is a zinc finger transcriptional activator that binds methylated DNA. The encoded protein can form homodimers or heterodimers through the zinc finger domains. In mouse, inhibition of this protein has been associated with apoptosis in some cell types. [provided by RefSeq, Jun 2010]

ZBTB38 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16071066).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB38	NM_001376113.1 linkuse as main transcript	c.86G>A	p.Arg29Gln	missense_variant	6/6	ENST00000321464.7	NP_001363042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB38	ENST00000321464.7 linkuse as main transcript	c.86G>A	p.Arg29Gln	missense_variant	6/6		NM_001376113.1	ENSP00000372635	P1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000401

AC:

AN:

249414

Hom.:

AF XY:

0.0000370

AC XY:

AN XY:

135306

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.0000290

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:

0.0000707

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000383

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0000481

AC XY:

AN XY:

727246

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000468

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000579

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

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

Dec 03, 2021

The c.86G>A (p.R29Q) alteration is located in exon 8 (coding exon 1) of the ZBTB38 gene. This alteration results from a G to A substitution at nucleotide position 86, causing the arginine (R) at amino acid position 29 to be replaced by a glutamine (Q). 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

Uncertain

0.51

BayesDel_addAF

Benign

-0.084

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

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

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.91

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

M_CAP

Benign

0.011

MetaRNN

Benign

0.16

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

MetaSVM

Benign

-0.80

MutationAssessor

Benign

-0.62

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

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.55

N;N;.;D;N;N;N;.;N;N;N;N;N;N;.

REVEL

Benign

0.25

Sift

Benign

0.20

T;T;.;D;T;T;T;.;T;T;T;T;T;T;.

Sift4G

Benign

1.0

T;T;.;D;T;T;T;.;T;T;T;T;T;T;T

Polyphen

0.92

.;.;.;.;.;.;P;P;.;.;.;P;.;.;P

Vest4

0.48, 0.50, 0.50

MutPred

0.53

Gain of relative solvent accessibility (P = 0.1894);Gain of relative solvent accessibility (P = 0.1894);Gain of relative solvent accessibility (P = 0.1894);Gain of relative solvent accessibility (P = 0.1894);Gain of relative solvent accessibility (P = 0.1894);Gain of relative solvent accessibility (P = 0.1894);Gain of relative solvent accessibility (P = 0.1894);Gain of relative solvent accessibility (P = 0.1894);Gain of relative solvent accessibility (P = 0.1894);Gain of relative solvent accessibility (P = 0.1894);Gain of relative solvent accessibility (P = 0.1894);Gain of relative solvent accessibility (P = 0.1894);Gain of relative solvent accessibility (P = 0.1894);Gain of relative solvent accessibility (P = 0.1894);Gain of relative solvent accessibility (P = 0.1894);

MVP

0.44

MPC

1.4

ClinPred

0.14

GERP RS

5.2

Varity_R

0.20

gMVP

0.77

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