Variant 1-32593742-A-G 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_001040441.3(ZBTB8A):c.811A>G(p.Lys271Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000291 in 1,608,620 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00062 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

ZBTB8A
NM_001040441.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.35

Variant links:

Genes affected

ZBTB8A (HGNC:24172): (zinc finger and BTB domain containing 8A) Predicted to enable RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB8A links:

ENSG00000254553 (HGNC:):

ENSG00000254553 links:

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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=0.0053797066).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB8A	NM_001040441.3 linkuse as main transcript	c.811A>G	p.Lys271Glu	missense_variant	3/5	ENST00000373510.9	NP_001035531.2	Q96BR9-1
ZBTB8A	NM_001291496.2 linkuse as main transcript	c.811A>G	p.Lys271Glu	missense_variant	3/5		NP_001278425.1	Q96BR9D3DPQ1
ZBTB8A	NR_111980.2 linkuse as main transcript	n.229-1312A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZBTB8A	ENST00000373510.9 linkuse as main transcript	c.811A>G	p.Lys271Glu	missense_variant	3/5	1	NM_001040441.3	ENSP00000362609.3	Q96BR9-1
ZBTB8A	ENST00000316459.4 linkuse as main transcript	c.811A>G	p.Lys271Glu	missense_variant	3/5	1		ENSP00000317561.4	D3DPQ1
ENSG00000254553	ENST00000480336.1 linkuse as main transcript	n.*930A>G		non_coding_transcript_exon_variant	8/10	2		ENSP00000455300.1
ENSG00000254553	ENST00000480336.1 linkuse as main transcript	n.*930A>G		3_prime_UTR_variant	8/10	2		ENSP00000455300.1

Frequencies

GnomAD3 genomes

AF:

0.000624

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000549

AC:

135

AN:

245858

Hom.:

AF XY:

0.000541

AC XY:

AN XY:

132966

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00164

Gnomad ASJ exome

AF:

0.00319

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000341

Gnomad OTH exome

AF:

0.00184

GnomAD4 exome

AF:

0.000256

AC:

373

AN:

1456282

Hom.:

Cov.:

AF XY:

0.000262

AC XY:

190

AN XY:

724010

show subpopulations

Gnomad4 AFR exome

AF:

0.0000602

Gnomad4 AMR exome

AF:

0.00137

Gnomad4 ASJ exome

AF:

0.00306

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000166

Gnomad4 OTH exome

AF:

0.000648

GnomAD4 genome

AF:

0.000624

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.000671

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000375

Hom.:

Bravo

AF:

0.000831

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000404

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000415

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

Nov 10, 2022

The c.811A>G (p.K271E) alteration is located in exon 3 (coding exon 1) of the ZBTB8A gene. This alteration results from a A to G substitution at nucleotide position 811, causing the lysine (K) at amino acid position 271 to be replaced by a glutamic acid (E). 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

0.13

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.0076

.;T

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.30

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.66

.;T

M_CAP

Benign

0.0042

MetaRNN

Benign

0.0054

T;T

MetaSVM

Benign

-0.94

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.19

N;N

REVEL

Benign

0.041

Sift

Benign

0.93

T;T

Sift4G

Benign

0.87

T;T

Polyphen

0.015

.;B

Vest4

0.33

MVP

0.14

MPC

0.55

ClinPred

0.014

GERP RS

2.9

gMVP

0.41

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