Variant 9-126833308-C-T 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_014007.4(ZBTB43):c.799C>T(p.His267Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 6.8e-7 ( 0 hom. )

Consequence

ZBTB43
NM_014007.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.05

Variant links:

Genes affected

ZBTB43 (HGNC:17908): (zinc finger and BTB domain containing 43) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB43 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=0.20073274).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB43	NM_014007.4 linkuse as main transcript	c.799C>T	p.His267Tyr	missense_variant	3/3	ENST00000373464.5	NP_054726.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZBTB43	ENST00000373464.5 linkuse as main transcript	c.799C>T	p.His267Tyr	missense_variant	3/3	1	NM_014007.4	ENSP00000362563	P1
ZBTB43	ENST00000373457.1 linkuse as main transcript	c.799C>T	p.His267Tyr	missense_variant	1/1			ENSP00000362556	P1
ZBTB43	ENST00000449886.5 linkuse as main transcript	c.799C>T	p.His267Tyr	missense_variant	2/2	3		ENSP00000390344	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460686

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726570

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Feb 13, 2024

The c.799C>T (p.H267Y) alteration is located in exon 3 (coding exon 1) of the ZBTB43 gene. This alteration results from a C to T substitution at nucleotide position 799, causing the histidine (H) at amino acid position 267 to be replaced by a tyrosine (Y). 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

0.17

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.17

T;T;T

Eigen

Benign

0.015

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.80

T;.;.

M_CAP

Benign

0.0037

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

L;L;L

MutationTaster

Benign

0.88

D;D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.13

Sift

Benign

0.038

D;D;D

Sift4G

Uncertain

0.019

D;D;D

Polyphen

0.17

B;B;B

Vest4

0.37

MutPred

0.64

Gain of phosphorylation at H267 (P = 0.0097);Gain of phosphorylation at H267 (P = 0.0097);Gain of phosphorylation at H267 (P = 0.0097);

MVP

0.10

MPC

0.88

ClinPred

0.45

GERP RS

5.4

Varity_R

0.28

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over