Variant 10-43644783-T-C 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_006973.3(ZNF32):c.89A>G(p.His30Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,603,962 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: 𝑓 0.000085 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

ZNF32
NM_006973.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.55

Variant links:

Genes affected

ZNF32 (HGNC:13095): (zinc finger protein 32) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF32 links:

ZNF32-AS3 (HGNC:):

ZNF32-AS3 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=0.08797473).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF32	NM_006973.3 linkuse as main transcript	c.89A>G	p.His30Arg	missense_variant	3/3	ENST00000374433.7	NP_008904.1	P17041A0A024R7T7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF32	ENST00000374433.7 linkuse as main transcript	c.89A>G	p.His30Arg	missense_variant	3/3	1	NM_006973.3	ENSP00000363556.2		P17041

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000176

AC:

AN:

238934

Hom.:

AF XY:

0.000131

AC XY:

AN XY:

129514

show subpopulations

Gnomad AFR exome

AF:

0.0000649

Gnomad AMR exome

AF:

0.000275

Gnomad ASJ exome

AF:

0.00233

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000551

Gnomad OTH exome

AF:

0.000867

GnomAD4 exome

AF:

0.000125

AC:

181

AN:

1451738

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

721722

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

Gnomad4 AMR exome

AF:

0.000256

Gnomad4 ASJ exome

AF:

0.00284

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000650

Gnomad4 OTH exome

AF:

0.000317

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000217

Hom.:

Bravo

AF:

0.000125

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000456

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000148

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

Jul 28, 2021

The c.89A>G (p.H30R) alteration is located in exon 3 (coding exon 2) of the ZNF32 gene. This alteration results from a A to G substitution at nucleotide position 89, causing the histidine (H) at amino acid position 30 to be replaced by an arginine (R). 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

0.089

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.050

T;T

Eigen

Benign

0.011

Eigen_PC

Benign

0.094

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.71

.;T

M_CAP

Benign

0.0041

MetaRNN

Benign

0.088

T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.0

N;N

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.27

N;N

REVEL

Benign

0.10

Sift

Benign

0.056

T;T

Sift4G

Benign

0.24

T;T

Polyphen

0.82

P;P

Vest4

0.57

MVP

0.088

MPC

0.78

ClinPred

0.039

GERP RS

4.1

Varity_R

0.11

gMVP

0.49

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