rs3745672

Variant names:

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

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-4 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -4 classification points (ACGS-UK Somatic Oncogenicity v2025). B1_Strong

The NM_001308348.2(ZNF433):c.-16A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The gene ZNF433 is a tumor suppressor gene (CancerMine: 1 TSG, 1 driver citations). The gene ZNF433 is a cancer driver gene (CancerMine: 1 TSG, 1 driver citations). The variant allele was found at a cumulative frequency of 0.0387 (AC=60,731) in the gnomAD database across 1,569,724 control chromosomes, including 1,832 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.159. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. 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)

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -4 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	B1High frequency in general population		GnomAD effective popmax AF >1% — B1 stand-alone benign; GnomAD effective popmax AF = 0.159 — exceeds 1% threshold (B1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_001308348.2. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF433	NM_001308348.2	MANE Select	c.-16A>G		5_prime_UTR	Exon 1 of 4	NP_001295277.1	F8VTV7
	ZNF433	NM_001080411.3		c.-16A>G		5_prime_UTR	Exon 1 of 4	NP_001073880.1	Q8N7K0-1
	ZNF433	NM_001308346.2		c.-78A>G		5_prime_UTR	Exon 1 of 5	NP_001295275.1	F8W0C9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF433	ENST00000550507.7	TSL:2 MANE Select	c.-16A>G		5_prime_UTR	Exon 1 of 4	ENSP00000448099.2	F8VTV7
	ZNF433	ENST00000419886.7	TSL:1	c.-159A>G		5_prime_UTR	Exon 1 of 5	ENSP00000393416.2	Q8N7K0-2
	ENSG00000286098	ENST00000652448.1		c.-94+33733T>C		intron	N/A	ENSP00000498410.1	A0A494C069

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 6 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.0704	AC:10700	Hom:609	AN:152080	Cov:32
GnomAD2 exomes	AF: 0.0401	AC:7179	Hom:	AN:178944	Cov:
GnomAD4 exome	AF: 0.0353	AC:50015	Hom:1219	AN:1417526	Cov:31
GnomAD4 genome	AF: 0.0704	AC:10716	Hom:613	AN:152198	Cov:32
TOPMed (Bravo)	AF: 0.0723	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.0445	AC:15475	Hom:563	AN:347684	Cov:
Local & regional cohorts 11 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.0692	AC:162	Hom:8	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.0216	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.0367	AC:11	Hom:	AN:300	Cov:
ESP6500 (Exome Variant Server)	AF: 0.0656	AC:814	Hom:	AN:12402	Cov:
GenomeAsia100K	AF: 0.0300	AC:104	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.0280	AC:203	Hom:	AN:7222	Cov:
Qatari Genome	AF: 0.0795	AC:14	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.0244	AC:2986	Hom:33	AN:122334	Cov:
Turkish Variome	AF: 0.0399	AC:263	Hom:8	AN:6588	Cov:
UK10K	AF: 0.0337	AC:255	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.0224	AC:201	Hom:2	AN:8960	Cov:

Showing 17 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
BipEx(Bipolar disorder (including schizoaffective))	0.0320	909	28414	0.0324	933	28828
SCHEMA(Schizophrenia)	0.0785	8764	111642	0.0774	14519	187676

Showing 2 cohortsAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated prediction	Prediction	Score
AlphaGenome AVI	Benign	-	9.7
BayesDel_noAF	Benign	-	-0.81
CADD	Benign	-	7.7
DANN	Benign	-	0.68
GPN-Star LLR	N/A	-	-2.9
GPN-Star score	N/A	-	2.9
Mutation Taster	N/A	polymorphism (auto)	299/1
PhyloP100	Benign	-	-0.34
PromoterAI	N/A	Neutral	0.12

Showing 9 of 9 scores

Splicing Scores

Algorithm	Calibrated prediction	Prediction	Score
Pangolin (max)	Benign	-	0.060
SpliceAI score (max)	Benign	- Details are displayed if max score is > 0.2	0.020

Showing 2 of 2 scores

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3745672;

hg19: chr19-12146370;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar