Variant 3-141443709-G-A 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_001376113.1(ZBTB38):c.1321G>A(p.Gly441Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000675 in 1,614,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

ZBTB38
NM_001376113.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.40

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 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=0.04736355).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB38	NM_001376113.1 linkuse as main transcript	c.1321G>A	p.Gly441Arg	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.1321G>A	p.Gly441Arg	missense_variant	6/6		NM_001376113.1	ENSP00000372635	P1

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000109

AC:

AN:

246896

Hom.:

AF XY:

0.000112

AC XY:

AN XY:

134172

show subpopulations

Gnomad AFR exome

AF:

0.000131

Gnomad AMR exome

AF:

0.000407

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000720

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.0000684

AC:

100

AN:

1461714

Hom.:

Cov.:

AF XY:

0.0000619

AC XY:

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000692

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000422

Hom.:

Bravo

AF:

0.0000604

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000243

AC:

ExAC

AF:

0.0000828

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

Jul 11, 2023

The c.1321G>A (p.G441R) 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 1321, causing the glycine (G) at amino acid position 441 to be replaced by an arginine (R). 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

0.14

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0083

T;.;T;T;T;T

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.81

T;T;.;.;.;T

M_CAP

Benign

0.0063

MetaRNN

Benign

0.047

T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.8

.;.;L;L;L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

0.22

.;N;N;.;N;.

REVEL

Benign

0.090

Sift

Benign

0.040

.;D;T;.;T;.

Sift4G

Benign

0.53

.;T;T;.;T;T

Polyphen

0.50

.;.;P;P;P;P

Vest4

0.13, 0.13, 0.13

MutPred

0.61

Gain of phosphorylation at S438 (P = 0.1234);Gain of phosphorylation at S438 (P = 0.1234);Gain of phosphorylation at S438 (P = 0.1234);Gain of phosphorylation at S438 (P = 0.1234);Gain of phosphorylation at S438 (P = 0.1234);Gain of phosphorylation at S438 (P = 0.1234);

MVP

0.14

MPC

0.51

ClinPred

0.011

GERP RS

2.4

Varity_R

0.025

gMVP

0.37

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