Variant 19-35714952-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_014383.3(ZBTB32):c.326G>A(p.Cys109Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000139 in 1,435,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZBTB32
NM_014383.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.19

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.794

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZBTB32	NM_014383.3 linkuse as main transcript	c.326G>A	p.Cys109Tyr	missense_variant	3/7	ENST00000392197.7	NP_055198.1
ZBTB32	NM_001316902.2 linkuse as main transcript	c.6-511G>A		intron_variant			NP_001303831.1
ZBTB32	NM_001316903.2 linkuse as main transcript	c.-86-511G>A		intron_variant			NP_001303832.1
ZBTB32	XM_017026591.2 linkuse as main transcript	c.6-511G>A		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.326G>A	p.Cys109Tyr	missense_variant	3/7	5	NM_014383.3	ENSP00000376035	P1
ZBTB32	ENST00000262630.7 linkuse as main transcript	c.326G>A	p.Cys109Tyr	missense_variant	2/6	1		ENSP00000262630	P1
ZBTB32	ENST00000481182.1 linkuse as main transcript	c.326G>A	p.Cys109Tyr	missense_variant, NMD_transcript_variant	2/4	1		ENSP00000433657
ZBTB32	ENST00000426659.6 linkuse as main transcript	c.-86-511G>A		intron_variant		3		ENSP00000466524

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1435860

Hom.:

Cov.:

AF XY:

0.00000281

AC XY:

AN XY:

712658

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:

0.00000182

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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 16, 2024

The c.326G>A (p.C109Y) alteration is located in exon 2 (coding exon 1) of the ZBTB32 gene. This alteration results from a G to A substitution at nucleotide position 326, causing the cysteine (C) at amino acid position 109 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

Pathogenic

0.85

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.86

D;D

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.78

.;T

M_CAP

Benign

0.022

MetaRNN

Pathogenic

0.79

D;D

MetaSVM

Benign

-0.67

MutationAssessor

Pathogenic

3.3

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-4.2

D;D

REVEL

Uncertain

0.33

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.99

D;D

Vest4

0.82

MutPred

0.43

Loss of catalytic residue at W110 (P = 5e-04);Loss of catalytic residue at W110 (P = 5e-04);

MVP

0.62

MPC

0.54

ClinPred

0.99

GERP RS

4.8

Varity_R

0.92

gMVP

0.53

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