NM_001308348.2:c.-16A>G

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:

Genome browser will be placed here

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

GnomAD3 genomes

AF:

0.0704

AC:

10700

AN:

152080

Hom.:

609

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0353

AC XY:

24759

AN XY:

701064

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

2323

4645

6968

9290

11613

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1318

2636

3954

5272

6590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0704

AC:

10716

AN:

152198

Hom.:

613

Cov.:

AF XY:

0.0708

AC XY:

5268

AN XY:

74408

show subpopulations

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0312

AC:

2122

AN:

68000

Other (OTH)

AF:

0.0639

AC:

135

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

492

984

1477

1969

2461

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

106

212

318

424

530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0400

Hom.:

335

Bravo

AF:

0.0723

Asia WGS

AF:

0.0300

AC:

104

AN:

3478

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.0244

AC:

2986

AN:

122334

Turkish Variome

AF:

0.0399

AC:

263

AN:

6588

Hom.:

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.0224

AC:

201

AN:

8960

Hom.:

ABraOM SABE-WGS-1171

AF:

0.0692

AC:

162

AN:

2342

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.7

(source)

DANN

Benign

0.68

PhyloP100

-0.34

PromoterAI

0.12

Neutral

(source)

Mutation Taster

=299/1

polymorphism (auto)

(source)

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

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

Age Distribution

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over