Variant 7-100072186-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_032924.5(ZNF3):c.298C>G(p.Gln100Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000157 in 1,595,474 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 2 hom. )

Consequence

ZNF3
NM_032924.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0730

Variant links:

Genes affected

ZNF3 (HGNC:13089): (zinc finger protein 3) Enables identical protein binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF3 links:

ZNF3 (HGNC:):

ZNF3 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=0.008500427).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF3	NM_032924.5 linkuse as main transcript	c.298C>G	p.Gln100Glu	missense_variant	6/6	ENST00000299667.9	NP_116313.3	P17036-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF3	ENST00000299667.9 linkuse as main transcript	c.298C>G	p.Gln100Glu	missense_variant	6/6	1	NM_032924.5	ENSP00000299667.4		P17036-1

Frequencies

GnomAD3 genomes

AF:

0.000315

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000243

AC:

AN:

230746

Hom.:

AF XY:

0.000295

AC XY:

AN XY:

125426

show subpopulations

Gnomad AFR exome

AF:

0.000132

Gnomad AMR exome

AF:

0.000680

Gnomad ASJ exome

AF:

0.00124

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000186

Gnomad OTH exome

AF:

0.000544

GnomAD4 exome

AF:

0.000141

AC:

204

AN:

1443214

Hom.:

Cov.:

AF XY:

0.000153

AC XY:

110

AN XY:

717634

show subpopulations

Gnomad4 AFR exome

AF:

0.000249

Gnomad4 AMR exome

AF:

0.000562

Gnomad4 ASJ exome

AF:

0.000914

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000777

Gnomad4 OTH exome

AF:

0.000521

GnomAD4 genome

AF:

0.000309

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.000416

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000336

Hom.:

Bravo

AF:

0.000306

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000232

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

Jul 13, 2021

The c.298C>G (p.Q100E) alteration is located in exon 6 (coding exon 4) of the ZNF3 gene. This alteration results from a C to G substitution at nucleotide position 298, causing the glutamine (Q) at amino acid position 100 to be replaced by a glutamic acid (E). 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

0.060

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.20

DEOGEN2

Benign

0.013

T;T;T;T;T;T;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.0057

LIST_S2

Benign

0.13

.;T;.;T;.;T;T;T

M_CAP

Benign

0.0026

MetaRNN

Benign

0.0085

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.32

N;N;N;.;.;.;.;.

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.17

N;N;N;N;N;N;N;N

REVEL

Benign

0.033

Sift

Benign

0.11

T;T;T;T;T;T;T;T

Sift4G

Benign

0.64

T;T;T;.;.;.;.;.

Polyphen

0.0

B;B;B;.;.;.;.;.

Vest4

0.20

MutPred

0.23

Gain of solvent accessibility (P = 0.0421);Gain of solvent accessibility (P = 0.0421);Gain of solvent accessibility (P = 0.0421);.;Gain of solvent accessibility (P = 0.0421);Gain of solvent accessibility (P = 0.0421);.;Gain of solvent accessibility (P = 0.0421);

MVP

0.13

MPC

0.33

ClinPred

0.0050

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.062

gMVP

0.051

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