Variant 16-4752473-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_021646.4(ZNF500):c.1346G>A(p.Gly449Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000614 in 1,544,834 control chromosomes in the GnomAD database, including 2 homozygotes. 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: 𝑓 0.00049 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00063 ( 2 hom. )

Consequence

ZNF500
NM_021646.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.190

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008656621).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF500	NM_021646.4 linkuse as main transcript	c.1346G>A	p.Gly449Asp	missense_variant	6/6	ENST00000219478.11	NP_067678.1
ZNF500	XM_005255243.5 linkuse as main transcript	c.995G>A	p.Gly332Asp	missense_variant	5/5		XP_005255300.1
ZNF500	NM_001303450.2 linkuse as main transcript	c.1297+49G>A		intron_variant			NP_001290379.1
ZNF500	XM_011522453.3 linkuse as main transcript	c.1297+49G>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.1346G>A	p.Gly449Asp	missense_variant	6/6	2	NM_021646.4	ENSP00000219478	P1	O60304-1

Frequencies

GnomAD3 genomes

AF:

0.000486

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

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:

0.000632

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000555

AC:

AN:

149484

Hom.:

AF XY:

0.000395

AC XY:

AN XY:

81060

show subpopulations

Gnomad AFR exome

AF:

0.000134

Gnomad AMR exome

AF:

0.00139

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:

0.000654

Gnomad OTH exome

AF:

0.00160

GnomAD4 exome

AF:

0.000628

AC:

875

AN:

1392586

Hom.:

Cov.:

AF XY:

0.000555

AC XY:

382

AN XY:

687966

show subpopulations

Gnomad4 AFR exome

AF:

0.0000629

Gnomad4 AMR exome

AF:

0.00135

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000125

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000735

Gnomad4 OTH exome

AF:

0.000482

GnomAD4 genome

AF:

0.000486

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.000416

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000632

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000634

Hom.:

Bravo

AF:

0.000578

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.000357

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

May 01, 2023

The c.1346G>A (p.G449D) 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 1346, causing the glycine (G) at amino acid position 449 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

0.86

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.058

Eigen

Benign

0.044

Eigen_PC

Benign

0.0066

FATHMM_MKL

Benign

0.20

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.012

MetaRNN

Benign

0.0087

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.9

REVEL

Benign

0.12

Sift

Benign

0.14

Sift4G

Benign

0.075

Polyphen

0.99

Vest4

0.22

MVP

0.24

MPC

0.31

ClinPred

0.070

GERP RS

4.2

Varity_R

0.22

gMVP

0.10

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