chr19-12035555-T-C

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, Jul 2025]

ENSG00000286098 (HGNC:):

ZNF433-AS1 (HGNC:53776): ()

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	Prot: NP_001295277.1 UniProt:
	ZNF433 NM_001080411.3		c.-16A>G	5_prime_UTR	Exon 1 of 4	Prot: NP_001073880.1 UniProt:
	ZNF433 NM_001308346.2		c.-78A>G	5_prime_UTR	Exon 1 of 5	Prot: NP_001295275.1 UniProt:

ZNF433 NM_001308348.2

MANE Select

HGVSc / HGVSpc.-16A>G

Exon rankExon 1 of 4

5_prime_UTR

Prot: NP_001295277.1UniProt: F8VTV7

ZNF433 NM_001080411.3

HGVSc / HGVSpc.-16A>G

Exon rankExon 1 of 4

5_prime_UTR

Prot: NP_001073880.1UniProt: Q8N7K0-1

ZNF433 NM_001308346.2

HGVSc / HGVSpc.-78A>G

Exon rankExon 1 of 5

5_prime_UTR

Prot: NP_001295275.1UniProt: F8W0C9

Ensembl Transcripts

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

ZNF433 ENST00000550507.7

TSL:2MANE Select

HGVSc / HGVSpc.-16A>G

Exon rankExon 1 of 4

5_prime_UTR

Prot: ENSP00000448099.2UniProt: F8VTV7

ZNF433 ENST00000419886.7

TSL:1

HGVSc / HGVSpc.-159A>G

Exon rankExon 1 of 5

5_prime_UTR

Prot: ENSP00000393416.2UniProt: Q8N7K0-2

ENSG00000286098 ENST00000652448.1

HGVSc / HGVSpc.-94+33733T>C

Exon rankIntron 2 of 4

intron

Prot: ENSP00000498410.1UniProt: 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 pred.	Score	Prediction
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	299/1	polymorphism (auto)
PhyloP100	Benign	-0.34
PromoterAI	N/A	0.12	Neutral

Showing 9 of 9 scores

Splicing Scores

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

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.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs3745672;

hg19: chr19-12146370;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar