rs3745672

Variant names:

• chr19-12035555-T-C
• rs3745672
• NM_001308348.2:c.-16A>G

Variant summary

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

The NM_001308348.2(ZNF433):​c.-16A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0387 in 1,569,724 control chromosomes in the GnomAD database, including 1,832 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.070 (613 hom., cov: 32)
  • Exomes 𝑓: 0.035 (1219 hom.)
• Consequence: ZNF433 NM_001308348.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335
• Publications: 32 publications found

Genes affected

ZNF433 (HGNC:20811): (zinc finger protein 433) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription 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]

ENSG00000286098 (HGNC:):

ZNF433-AS1 (HGNC:53776): (ZNF433 and ZNF878 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF433	NM_001308348.2	c.-16A>G		5_prime_UTR_variant	Exon 1 of 4	ENST00000550507.7	NP_001295277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF433	ENST00000550507.7	c.-16A>G		5_prime_UTR_variant	Exon 1 of 4	2	NM_001308348.2	ENSP00000448099.2
ENSG00000286098	ENST00000652448.1	c.-94+33733T>C		intron_variant	Intron 2 of 4			ENSP00000498410.1
ENSG00000257355	ENST00000547473.1	n.191+10813A>G		intron_variant	Intron 3 of 4	4		ENSP00000458124.1

Frequencies

GnomAD3 genomes AF: 0.0704 AC: 10700 AN: 152080 Hom.: 609 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.0419

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.0218

Gnomad SAS AF: 0.0437

Gnomad FIN AF: 0.0614

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0312

Gnomad OTH AF: 0.0645

GnomAD2 exomes AF: 0.0401 AC: 7179 AN: 178944 AF XY: 0.0393

Gnomad AFR exome AF: 0.153

Gnomad AMR exome AF: 0.0277

Gnomad ASJ exome AF: 0.0190

Gnomad EAS exome AF: 0.0240

Gnomad FIN exome AF: 0.0553

Gnomad NFE exome AF: 0.0306

Gnomad OTH exome AF: 0.0388

GnomAD4 exome AF: 0.0353 AC: 50015 AN: 1417526 Hom.: 1219 Cov.: 31 AF XY: 0.0353 AC XY: 24759 AN XY: 701064

African (AFR) AF: 0.158 AC: 5076 AN: 32160

American (AMR) AF: 0.0294 AC: 1125 AN: 38224

Ashkenazi Jewish (ASJ) AF: 0.0186 AC: 472 AN: 25408

East Asian (EAS) AF: 0.0252 AC: 932 AN: 36990

South Asian (SAS) AF: 0.0441 AC: 3549 AN: 80410

European-Finnish (FIN) AF: 0.0542 AC: 2726 AN: 50258

Middle Eastern (MID) AF: 0.0607 AC: 347 AN: 5712

European-Non Finnish (NFE) AF: 0.0307 AC: 33496 AN: 1089638

Other (OTH) AF: 0.0390 AC: 2292 AN: 58726

GnomAD4 genome AF: 0.0704 AC: 10716 AN: 152198 Hom.: 613 Cov.: 32 AF XY: 0.0708 AC XY: 5268 AN XY: 74408

African (AFR) AF: 0.162 AC: 6736 AN: 41512

American (AMR) AF: 0.0418 AC: 640 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 65 AN: 3470

East Asian (EAS) AF: 0.0217 AC: 112 AN: 5170

South Asian (SAS) AF: 0.0435 AC: 210 AN: 4826

European-Finnish (FIN) AF: 0.0614 AC: 651 AN: 10604

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0312 AC: 2122 AN: 68000

Other (OTH) AF: 0.0639 AC: 135 AN: 2114

Alfa AF: 0.0400 Hom.: 335

Bravo AF: 0.0723

Asia WGS AF: 0.0300 AC: 104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.7
DANN	Benign	0.68
PhyloP100		-0.34
PromoterAI		0.12	Neutral
Mutation Taster		=299/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3745672; hg19: chr19-12146370;