Variant chr1-32593099-T-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.168T>G(p.Asn56Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,614,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

ZBTB8A
NM_001040441.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0880

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:

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=0.049200535).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB8A	NM_001040441.3 linkuse as main transcript	c.168T>G	p.Asn56Lys	missense_variant	3/5	ENST00000373510.9	NP_001035531.2	Q96BR9-1
ZBTB8A	NM_001291496.2 linkuse as main transcript	c.168T>G	p.Asn56Lys	missense_variant	3/5		NP_001278425.1	Q96BR9D3DPQ1
ZBTB8A	NR_111980.2 linkuse as main transcript	n.229-1955T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZBTB8A	ENST00000373510.9 linkuse as main transcript	c.168T>G	p.Asn56Lys	missense_variant	3/5	1	NM_001040441.3	ENSP00000362609.3	Q96BR9-1
ZBTB8A	ENST00000316459.4 linkuse as main transcript	c.168T>G	p.Asn56Lys	missense_variant	3/5	1		ENSP00000317561.4	D3DPQ1
ENSG00000254553	ENST00000480336.1 linkuse as main transcript	n.*287T>G		non_coding_transcript_exon_variant	8/10	2		ENSP00000455300.1
ENSG00000254553	ENST00000480336.1 linkuse as main transcript	n.*287T>G		3_prime_UTR_variant	8/10	2		ENSP00000455300.1

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000676

AC:

AN:

251452

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.000173

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.000112

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:

0.00

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000204

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000697

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000263

Hom.:

Bravo

AF:

0.000170

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000741

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 25, 2024

The c.168T>G (p.N56K) alteration is located in exon 3 (coding exon 1) of the ZBTB8A gene. This alteration results from a T to G substitution at nucleotide position 168, causing the asparagine (N) at amino acid position 56 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

0.31

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.17

.;T

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.86

.;D

M_CAP

Benign

0.036

MetaRNN

Benign

0.049

T;T

MetaSVM

Benign

-0.90

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.71

N;N

REVEL

Benign

0.13

Sift

Benign

0.24

T;T

Sift4G

Benign

0.40

T;T

Polyphen

0.0040

.;B

Vest4

0.25

MutPred

0.48

Gain of solvent accessibility (P = 0.0062);Gain of solvent accessibility (P = 0.0062);

MVP

0.32

MPC

0.56

ClinPred

0.030

GERP RS

-3.0

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