dbSNP rs3885179: ZNF333:p.Ala251Glu (chr19-14717018-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032433.4(ZNF333):c.752C>A(p.Ala251Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0423 in 1,611,552 control chromosomes in the GnomAD database, including 1,649 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.041 ( 145 hom., cov: 32)

Exomes 𝑓: 0.042 ( 1504 hom. )

Consequence

ZNF333
NM_032433.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.143

Publications

13 publications found

Variant links:

Genes affected

ZNF333 (HGNC:15624): (zinc finger protein 333) 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. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF333 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040817857).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF333	NM_032433.4 link	c.752C>A	p.Ala251Glu	missense_variant	Exon 10 of 12	ENST00000292530.11	NP_115809.1	Q96JL9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF333	ENST00000292530.11 link	c.752C>A	p.Ala251Glu	missense_variant	Exon 10 of 12	1	NM_032433.4	ENSP00000292530.5		Q96JL9-1

Frequencies

GnomAD3 genomes

AF:

0.0413

AC:

6285

AN:

152090

Hom.:

145

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0381

Gnomad AMI

AF:

0.0308

Gnomad AMR

AF:

0.0204

Gnomad ASJ

AF:

0.0384

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.0659

Gnomad FIN

AF:

0.0540

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0400

Gnomad OTH

AF:

0.0407

GnomAD2 exomes

AF:

0.0454

AC:

11228

AN:

247418

AF XY:

0.0472

show subpopulations

Gnomad AFR exome

AF:

0.0364

Gnomad AMR exome

AF:

0.0132

Gnomad ASJ exome

AF:

0.0324

Gnomad EAS exome

AF:

0.112

Gnomad FIN exome

AF:

0.0552

Gnomad NFE exome

AF:

0.0398

Gnomad OTH exome

AF:

0.0440

GnomAD4 exome

AF:

0.0424

AC:

61805

AN:

1459344

Hom.:

1504

Cov.:

AF XY:

0.0431

AC XY:

31244

AN XY:

725690

show subpopulations

African (AFR)

AF:

0.0384

AC:

1284

AN:

33452

American (AMR)

AF:

0.0145

AC:

645

AN:

44570

Ashkenazi Jewish (ASJ)

AF:

0.0318

AC:

827

AN:

26046

East Asian (EAS)

AF:

0.0957

AC:

3793

AN:

39644

South Asian (SAS)

AF:

0.0651

AC:

5578

AN:

85644

European-Finnish (FIN)

AF:

0.0575

AC:

3061

AN:

53270

Middle Eastern (MID)

AF:

0.0554

AC:

319

AN:

5762

European-Non Finnish (NFE)

AF:

0.0393

AC:

43602

AN:

1110656

Other (OTH)

AF:

0.0447

AC:

2696

AN:

60300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

2967

5935

8902

11870

14837

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1702

3404

5106

6808

8510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0413

AC:

6288

AN:

152208

Hom.:

145

Cov.:

AF XY:

0.0430

AC XY:

3196

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0381

AC:

1583

AN:

41540

American (AMR)

AF:

0.0203

AC:

311

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0384

AC:

133

AN:

3468

East Asian (EAS)

AF:

0.103

AC:

532

AN:

5168

South Asian (SAS)

AF:

0.0657

AC:

317

AN:

4824

European-Finnish (FIN)

AF:

0.0540

AC:

572

AN:

10584

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0400

AC:

2720

AN:

68018

Other (OTH)

AF:

0.0402

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

322

645

967

1290

1612

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0417

Hom.:

469

Bravo

AF:

0.0390

TwinsUK

AF:

0.0410

AC:

152

ALSPAC

AF:

0.0410

AC:

158

ESP6500AA

AF:

0.0334

AC:

147

ESP6500EA

AF:

0.0408

AC:

351

ExAC

AF:

0.0468

AC:

5678

Asia WGS

AF:

0.0810

AC:

282

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.9

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.00083

.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.58

T;T

MetaRNN

Benign

0.0041

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.095

N;N

PhyloP100

-0.14

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.040

Sift

Uncertain

0.017

D;D

Sift4G

Benign

0.35

T;T

Polyphen

0.17

.;B

Vest4

0.19

MPC

0.44

ClinPred

0.038

GERP RS

-4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.070

gMVP

0.11

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over