chr19-14717018-C-A

Variant names:

• chr19-14717018-C-A
• rs3885179
• NM_032433.4:c.752C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.143
• Publications: 13 publications found

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]

ACMG classification

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	c.752C>A	p.Ala251Glu	missense_variant	Exon 10 of 12	ENST00000292530.11	NP_115809.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0413 AC: 6285 AN: 152090 Hom.: 145 Cov.: 32

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

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.: 30 AF XY: 0.0431 AC XY: 31244 AN XY: 725690

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

GnomAD4 genome AF: 0.0413 AC: 6288 AN: 152208 Hom.: 145 Cov.: 32 AF XY: 0.0430 AC XY: 3196 AN XY: 74410

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: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0400 AC: 2720 AN: 68018

Other (OTH) AF: 0.0402 AC: 85 AN: 2112

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	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.9
DANN	Benign	0.90
DEOGEN2	Benign	0.00083	.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.58	T;T
MetaRNN	Benign	0.0041	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.095	N;N
PhyloP100		-0.14
PrimateAI	Benign	0.23	T
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	T
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)

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

Other links and lift over

dbSNP: rs3885179; hg19: chr19-14827830; COSMIC: COSV52885432; COSMIC: COSV52885432;