Variant 9-122919392-C-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_020924.4(ZBTB26):c.543G>T(p.Gln181His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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

ZBTB26
NM_020924.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.04

Variant links:

Genes affected

ZBTB26 (HGNC:23383): (zinc finger and BTB domain containing 26) Enables identical protein binding activity and sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB26 links:

Genome browser will be placed here

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=0.1853678).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB26	NM_020924.4 linkuse as main transcript	c.543G>T	p.Gln181His	missense_variant	2/2	ENST00000373656.4	NP_065975.1	Q9HCK0
ZBTB26	NM_001304363.2 linkuse as main transcript	c.543G>T	p.Gln181His	missense_variant	2/2		NP_001291292.1	Q9HCK0
ZBTB26	NM_001304364.2 linkuse as main transcript	c.543G>T	p.Gln181His	missense_variant	2/2		NP_001291293.1	Q9HCK0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB26	ENST00000373656.4 linkuse as main transcript	c.543G>T	p.Gln181His	missense_variant	2/2	1	NM_020924.4	ENSP00000362760.3		Q9HCK0
ZBTB26	ENST00000373654.1 linkuse as main transcript	c.543G>T	p.Gln181His	missense_variant	2/2	2		ENSP00000362758.1		Q9HCK0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251428

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

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:

0.00000137

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Jan 23, 2024

The c.543G>T (p.Q181H) alteration is located in exon 2 (coding exon 1) of the ZBTB26 gene. This alteration results from a G to T substitution at nucleotide position 543, causing the glutamine (Q) at amino acid position 181 to be replaced by a histidine (H). 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

0.32

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.043

T;T

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.82

.;T

M_CAP

Benign

0.0087

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.4

L;L

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.063

Sift

Benign

0.12

T;T

Sift4G

Benign

0.22

T;T

Polyphen

0.98

D;D

Vest4

0.18

MutPred

0.22

Loss of stability (P = 0.1136);Loss of stability (P = 0.1136);

MVP

0.57

MPC

1.1

ClinPred

0.33

GERP RS

5.5

Varity_R

0.20

gMVP

0.44

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