Variant 19-35715432-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_014383.3(ZBTB32):c.806C>T(p.Pro269Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000175 in 1,597,036 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: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

ZBTB32
NM_014383.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.262

Variant links:

Genes affected

ZBTB32 (HGNC:16763): (zinc finger and BTB domain containing 32) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific; identical protein binding activity; and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB32 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=0.13987672).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZBTB32	NM_014383.3 linkuse as main transcript	c.806C>T	p.Pro269Leu	missense_variant	3/7	ENST00000392197.7	NP_055198.1
ZBTB32	NM_001316902.2 linkuse as main transcript	c.6-31C>T		intron_variant			NP_001303831.1
ZBTB32	NM_001316903.2 linkuse as main transcript	c.-86-31C>T		intron_variant			NP_001303832.1
ZBTB32	XM_017026591.2 linkuse as main transcript	c.6-31C>T		intron_variant			XP_016882080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZBTB32	ENST00000392197.7 linkuse as main transcript	c.806C>T	p.Pro269Leu	missense_variant	3/7	5	NM_014383.3	ENSP00000376035	P1
ZBTB32	ENST00000262630.7 linkuse as main transcript	c.806C>T	p.Pro269Leu	missense_variant	2/6	1		ENSP00000262630	P1
ZBTB32	ENST00000481182.1 linkuse as main transcript	c.806C>T	p.Pro269Leu	missense_variant, NMD_transcript_variant	2/4	1		ENSP00000433657
ZBTB32	ENST00000426659.6 linkuse as main transcript	c.-86-31C>T		intron_variant		3		ENSP00000466524

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000522

AC:

AN:

230092

Hom.:

AF XY:

0.0000477

AC XY:

AN XY:

125814

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000528

Gnomad SAS exome

AF:

0.0000358

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000190

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000173

AC:

AN:

1444764

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

718944

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000404

Gnomad4 SAS exome

AF:

0.0000476

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000452

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000495

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

Nov 18, 2022

The c.806C>T (p.P269L) alteration is located in exon 2 (coding exon 1) of the ZBTB32 gene. This alteration results from a C to T substitution at nucleotide position 806, causing the proline (P) at amino acid position 269 to be replaced by a leucine (L). 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

Uncertain

0.56

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

T;T

Eigen

Benign

0.11

Eigen_PC

Benign

0.090

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.85

.;D

M_CAP

Benign

0.023

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.18

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

1.0

D;D

Vest4

0.19

MutPred

0.60

Loss of glycosylation at P269 (P = 0.039);Loss of glycosylation at P269 (P = 0.039);

MVP

0.70

MPC

0.35

ClinPred

0.24

GERP RS

5.3

Varity_R

0.11

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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