Genetic Variant ZNF432:c.-266G>A (chr19-52048768-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014650.4(ZNF432):c.-266G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,718 control chromosomes in the GnomAD database, including 2,181 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 0.15 ( 2174 hom., cov: 31)

Exomes 𝑓: 0.13 ( 7 hom. )

Consequence

ZNF432
NM_014650.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.492

Publications

32 publications found

Variant links:

Genes affected

ZNF432 (HGNC:20810): (zinc finger protein 432) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF432 links:

ENSG00000275055 (HGNC:):

ENSG00000275055 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014650.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZNF432	NM_014650.4	MANE Select	c.-266G>A	5_prime_UTR	Exon 1 of 5	NP_055465.1	O94892
ZNF432	NM_001322284.2		c.-352G>A	upstream_gene	N/A	NP_001309213.1	O94892
ZNF432	NM_001322285.1		c.-420G>A	upstream_gene	N/A	NP_001309214.1	O94892

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZNF432	ENST00000221315.10	TSL:1 MANE Select	c.-266G>A	5_prime_UTR	Exon 1 of 5	ENSP00000221315.4	O94892
ZNF432	ENST00000600368.5	TSL:5	c.-192-1708G>A	intron	N/A	ENSP00000471172.1	M0R0E2
ENSG00000275055	ENST00000614138.3	TSL:6	n.112C>T	non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22325

AN:

152064

Hom.:

2171

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0532

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.191

Gnomad ASJ

AF:

0.116

Gnomad EAS

AF:

0.378

Gnomad SAS

AF:

0.285

Gnomad FIN

AF:

0.165

Gnomad MID

AF:

0.169

Gnomad NFE

AF:

0.165

Gnomad OTH

AF:

0.156

GnomAD4 exome

AF:

0.134

AC:

AN:

536

Hom.:

Cov.:

AF XY:

0.115

AC XY:

AN XY:

340

show subpopulations

African (AFR)

AF:

0.167

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.250

AC:

AN:

European-Finnish (FIN)

AF:

0.157

AC:

AN:

236

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.100

AC:

AN:

250

Other (OTH)

AF:

0.154

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.147

AC:

22352

AN:

152182

Hom.:

2174

Cov.:

AF XY:

0.152

AC XY:

11290

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0532

AC:

2208

AN:

41538

American (AMR)

AF:

0.192

AC:

2932

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.116

AC:

402

AN:

3468

East Asian (EAS)

AF:

0.377

AC:

1946

AN:

5156

South Asian (SAS)

AF:

0.287

AC:

1388

AN:

4828

European-Finnish (FIN)

AF:

0.165

AC:

1747

AN:

10580

Middle Eastern (MID)

AF:

0.164

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.165

AC:

11225

AN:

67998

Other (OTH)

AF:

0.158

AC:

334

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

938

1876

2813

3751

4689

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

266

532

798

1064

1330

<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:

0.160

Hom.:

6222

Bravo

AF:

0.144

Asia WGS

AF:

0.322

AC:

1117

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.5

(source)

DANN

Benign

0.76

PhyloP100

-0.49

PromoterAI

0.056

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over