rs3745672

Variant names:

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_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 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.335

Publications

32 publications found

Variant links:

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]

ZNF433 links:

ENSG00000286098 (HGNC:):

ENSG00000286098 links:

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

ZNF433-AS1 links:

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new If you want to explore the variant's impact on the transcript NM_001308348.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

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

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.1590 — exceeds 5%% threshold (BA1 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

Gene	Transcript	Tags	HGVSc	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

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

Showing 17 sources

Case/control cohorts

Cohort	Cases			Controls
Cohort	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.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Case/control cohorts

ClinVar

Computational Scores

Splicing Scores

Publications

Other links and lift over