Variant 16-4752389-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_021646.4(ZNF500):c.1430G>A(p.Gly477Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000864 in 1,505,274 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 0.000039 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000052 ( 0 hom. )

Consequence

ZNF500
NM_021646.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.690

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:

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=0.095748514).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF500	NM_021646.4 linkuse as main transcript	c.1430G>A	p.Gly477Asp	missense_variant	6/6	ENST00000219478.11	NP_067678.1
ZNF500	XM_005255243.5 linkuse as main transcript	c.1079G>A	p.Gly360Asp	missense_variant	5/5		XP_005255300.1
ZNF500	NM_001303450.2 linkuse as main transcript	c.1297+133G>A		intron_variant			NP_001290379.1
ZNF500	XM_011522453.3 linkuse as main transcript	c.1297+133G>A		intron_variant			XP_011520755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF500	ENST00000219478.11 linkuse as main transcript	c.1430G>A	p.Gly477Asp	missense_variant	6/6	2	NM_021646.4	ENSP00000219478	P1	O60304-1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000164

AC:

AN:

122174

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

66014

show subpopulations

Gnomad AFR exome

AF:

0.000271

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.00000517

AC:

AN:

1353028

Hom.:

Cov.:

AF XY:

0.00000752

AC XY:

AN XY:

664588

show subpopulations

Gnomad4 AFR exome

AF:

0.000199

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:

0.0000178

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

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

Aug 13, 2021

The c.1430G>A (p.G477D) alteration is located in exon 6 (coding exon 5) of the ZNF500 gene. This alteration results from a G to A substitution at nucleotide position 1430, causing the glycine (G) at amino acid position 477 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

Benign

0.18

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

8.3

DANN

Uncertain

0.99

DEOGEN2

Benign

0.038

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.38

M_CAP

Benign

0.0077

MetaRNN

Benign

0.096

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.0

REVEL

Benign

0.035

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.033

Polyphen

0.92

Vest4

0.15

MutPred

0.36

Gain of solvent accessibility (P = 0.0354);

MVP

0.24

MPC

0.062

ClinPred

0.15

GERP RS

1.9

Varity_R

0.13

gMVP

0.087

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