rs3745672

Positions:

• chr19-12035555-T-C

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ZNF433	NM_001308348.2	c.-16A>G		5_prime_UTR_variant	1/4	ENST00000550507.7	NP_001295277.1

Ensembl

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

GnomAD3 exomes AF: 0.0401 AC: 7179 AN: 178944 Hom.: 246 AF XY: 0.0393 AC XY: 3775 AN XY: 96102

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 SAS exome AF: 0.0456

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

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.0294

Gnomad4 ASJ exome AF: 0.0186

Gnomad4 EAS exome AF: 0.0252

Gnomad4 SAS exome AF: 0.0441

Gnomad4 FIN exome AF: 0.0542

Gnomad4 NFE exome AF: 0.0307

Gnomad4 OTH exome AF: 0.0390

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

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.0418

Gnomad4 ASJ AF: 0.0187

Gnomad4 EAS AF: 0.0217

Gnomad4 SAS AF: 0.0435

Gnomad4 FIN AF: 0.0614

Gnomad4 NFE AF: 0.0312

Gnomad4 OTH AF: 0.0639

Alfa AF: 0.0369 Hom.: 194

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs3745672; hg19: chr19-12146370;