Variant 19-52034033-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_014650.4(ZNF432):c.1646G>A(p.Gly549Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ZNF432
NM_014650.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.198

Variant links:

Genes affected

ZNF432 (HGNC:20810): (zinc finger protein 432) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF432 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=0.14371458).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZNF432	NM_014650.4 linkuse as main transcript	c.1646G>A	p.Gly549Asp	missense_variant	5/5	ENST00000221315.10
ZNF432	NM_001322284.2 linkuse as main transcript	c.1646G>A	p.Gly549Asp	missense_variant	5/5
ZNF432	NM_001322285.1 linkuse as main transcript	c.1646G>A	p.Gly549Asp	missense_variant	5/5
ZNF432	XM_024451806.2 linkuse as main transcript	c.1358G>A	p.Gly453Asp	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF432	ENST00000221315.10 linkuse as main transcript	c.1646G>A	p.Gly549Asp	missense_variant	5/5	1	NM_014650.4	P1
ZNF432	ENST00000594154.5 linkuse as main transcript	c.1646G>A	p.Gly549Asp	missense_variant	5/5	1		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727222

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:

0.00000450

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

Jun 29, 2023

The c.1646G>A (p.G549D) alteration is located in exon 5 (coding exon 4) of the ZNF432 gene. This alteration results from a G to A substitution at nucleotide position 1646, causing the glycine (G) at amino acid position 549 to be replaced by an aspartic acid (D). 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

0.80

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.028

T;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.0018

LIST_S2

Benign

0.25

.;T

M_CAP

Benign

0.0014

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-2.3

.;N

REVEL

Benign

0.086

Sift

Uncertain

0.0010

.;D

Sift4G

Benign

0.098

T;T

Polyphen

0.41

B;B

Vest4

0.45

MutPred

0.59

Gain of ubiquitination at K553 (P = 0.0539);Gain of ubiquitination at K553 (P = 0.0539);

MVP

0.25

MPC

0.33

ClinPred

0.72

GERP RS

1.6

Varity_R

0.47

gMVP

0.090

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