Variant chr9-126880441-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001099270.4(ZBTB34):c.1042G>A(p.Glu348Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,294 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: 0.0000062 ( 0 hom. )

Consequence

ZBTB34
NM_001099270.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.33

Variant links:

Genes affected

ZBTB34 (HGNC:31446): (zinc finger and BTB domain containing 34) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB34 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1602355).

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB34	NM_001099270.4 linkuse as main transcript	c.1042G>A	p.Glu348Lys	missense_variant	2/2	ENST00000319119.5	NP_001092740.2	Q8NCN2
ZBTB34	NM_001395198.1 linkuse as main transcript	c.1072G>A	p.Glu358Lys	missense_variant	3/3		NP_001382127.1
ZBTB34	XM_047423402.1 linkuse as main transcript	c.1072G>A	p.Glu358Lys	missense_variant	3/3		XP_047279358.1
ZBTB34	XM_011518699.4 linkuse as main transcript	c.1042G>A	p.Glu348Lys	missense_variant	2/2		XP_011517001.1	Q8NCN2A0A0C4DFQ2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB34	ENST00000319119.5 linkuse as main transcript	c.1042G>A	p.Glu348Lys	missense_variant	2/2	1	NM_001099270.4	ENSP00000317534.4		A0A0C4DFQ2
ZBTB34	ENST00000695642.1 linkuse as main transcript	c.1072G>A	p.Glu358Lys	missense_variant	3/3			ENSP00000512077.1		A0A8Q3WKM1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000202

AC:

AN:

248132

Hom.:

AF XY:

0.0000371

AC XY:

AN XY:

134878

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:

0.0000445

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461294

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726920

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:

0.00000809

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000153

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

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

Dec 17, 2023

The c.1030G>A (p.E344K) alteration is located in exon 2 (coding exon 1) of the ZBTB34 gene. This alteration results from a G to A substitution at nucleotide position 1030, causing the glutamic acid (E) at amino acid position 344 to be replaced by a lysine (K). 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

0.27

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

.;T

Eigen

Benign

0.051

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.0088

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

.;L

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.75

N;N

REVEL

Benign

0.21

Sift

Benign

0.060

T;T

Sift4G

Benign

0.10

T;T

Polyphen

0.25

.;B

Vest4

0.41

MutPred

0.37

.;Gain of ubiquitination at E344 (P = 0.0022);

MVP

0.14

MPC

0.87

ClinPred

0.32

GERP RS

5.9

Varity_R

0.18

gMVP

0.55

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