Variant chr19-30443823-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014717.3(ZNF536):c.261G>C(p.Gln87His) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF536
NM_014717.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.41

Variant links:

Genes affected

ZNF536 (HGNC:29025): (zinc finger protein 536) The protein encoded by this gene is a highly conserved zinc finger protein. The encoded protein is most abundant in brain, where it negatively regulates neuronal differentiation. [provided by RefSeq, Sep 2015]

ZNF536 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35509974).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF536	NM_014717.3 linkuse as main transcript	c.261G>C	p.Gln87His	missense_variant	2/5	ENST00000355537.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF536	ENST00000355537.4 linkuse as main transcript	c.261G>C	p.Gln87His	missense_variant	2/5	1	NM_014717.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248162

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134734

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000548

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460852

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726736

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

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

Mar 15, 2024

The c.261G>C (p.Q87H) alteration is located in exon 2 (coding exon 1) of the ZNF536 gene. This alteration results from a G to C substitution at nucleotide position 261, causing the glutamine (Q) at amino acid position 87 to be replaced by a histidine (H). 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

0.23

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

T;.;T

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.36

T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

0.46

.;.;N

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.2

.;.;N

REVEL

Benign

0.17

Sift

Uncertain

0.0020

.;.;D

Sift4G

Benign

0.16

T;D;T

Polyphen

1.0

.;.;D

Vest4

0.53

MutPred

0.44

Loss of disorder (P = 0.0889);Loss of disorder (P = 0.0889);Loss of disorder (P = 0.0889);

MVP

0.21

MPC

1.8

ClinPred

0.90

GERP RS

4.6

Varity_R

0.38

gMVP

0.56

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