Variant chr3-141443634-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.1246G>A(p.Gly416Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,876 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: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZBTB38
NM_001376113.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.33

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:

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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=0.20436731).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB38	NM_001376113.1 link	c.1246G>A	p.Gly416Arg	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 link	c.1246G>A	p.Gly416Arg	missense_variant	6/6	6	NM_001376113.1	ENSP00000372635.5		Q8NAP3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

249038

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135104

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:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727240

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000828

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Jun 30, 2022

The c.1246G>A (p.G416R) 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 1246, causing the glycine (G) at amino acid position 416 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

Uncertain

0.39

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.046

T;.;T;T;T;T

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.75

T;T;.;.;.;T

M_CAP

Benign

0.0087

MetaRNN

Benign

0.20

T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.1

.;.;M;M;M;M

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-2.0

.;N;N;.;N;.

REVEL

Benign

0.13

Sift

Benign

0.038

.;D;D;.;D;.

Sift4G

Benign

0.098

.;T;T;.;T;T

Polyphen

0.78

.;.;P;P;P;P

Vest4

0.44, 0.48, 0.48

MutPred

0.19

Gain of solvent accessibility (P = 0.0971);Gain of solvent accessibility (P = 0.0971);Gain of solvent accessibility (P = 0.0971);Gain of solvent accessibility (P = 0.0971);Gain of solvent accessibility (P = 0.0971);Gain of solvent accessibility (P = 0.0971);

MVP

0.42

MPC

1.4

ClinPred

0.67

GERP RS

5.6

Varity_R

0.090

gMVP

0.38

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