Variant 16-4752821-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021646.4(ZNF500):c.998G>C(p.Gly333Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,614,268 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 0.00041 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

ZNF500
NM_021646.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.477

Variant links:

Genes affected

ZNF500 (HGNC:23716): (zinc finger protein 500) 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 cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF500 links:

ZNF500 (HGNC:):

ZNF500 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.006996691).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF500	NM_021646.4 linkuse as main transcript	c.998G>C	p.Gly333Ala	missense_variant	6/6	ENST00000219478.11	NP_067678.1	O60304-1
ZNF500	NM_001303450.2 linkuse as main transcript	c.998G>C	p.Gly333Ala	missense_variant	6/7		NP_001290379.1	O60304-2
ZNF500	XM_011522453.3 linkuse as main transcript	c.998G>C	p.Gly333Ala	missense_variant	6/7		XP_011520755.1
ZNF500	XM_005255243.5 linkuse as main transcript	c.647G>C	p.Gly216Ala	missense_variant	5/5		XP_005255300.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF500	ENST00000219478.11 linkuse as main transcript	c.998G>C	p.Gly333Ala	missense_variant	6/6	2	NM_021646.4	ENSP00000219478.5		O60304-1

Frequencies

GnomAD3 genomes

AF:

0.000407

AC:

AN:

152266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000139

AC:

AN:

251418

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000128

AC:

187

AN:

1461884

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00119

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000102

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.000407

AC:

AN:

152384

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000636

Hom.:

Bravo

AF:

0.000480

ESP6500AA

AF:

0.00205

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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 25, 2024

The c.998G>C (p.G333A) alteration is located in exon 6 (coding exon 5) of the ZNF500 gene. This alteration results from a G to C substitution at nucleotide position 998, causing the glycine (G) at amino acid position 333 to be replaced by an alanine (A). 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

0.20

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.80

DANN

Benign

0.83

DEOGEN2

Benign

0.019

T;.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.42

T;T;T

M_CAP

Benign

0.0015

MetaRNN

Benign

0.0070

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.73

N;N;.

PrimateAI

Uncertain

0.60

PROVEAN

Benign

0.82

N;N;.

REVEL

Benign

0.045

Sift

Benign

0.94

T;T;.

Sift4G

Benign

0.71

T;T;T

Polyphen

0.0010

B;.;.

Vest4

0.027

MVP

0.048

MPC

0.042

ClinPred

0.0058

GERP RS

-0.92

Varity_R

0.044

gMVP

0.044

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