dbSNP rs6509616: ZNF432:p.Ser218Ser (chr19-52035025-A-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_014650.4(ZNF432):c.654T>G(p.Ser218Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0278 in 1,613,930 control chromosomes in the GnomAD database, including 956 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 0.048 ( 257 hom., cov: 33)

Exomes 𝑓: 0.026 ( 699 hom. )

Consequence

ZNF432
NM_014650.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.09

Publications

5 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP7

Synonymous conserved (PhyloP=-2.09 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
ZNF432	NM_014650.4 link	c.654T>G	p.Ser218Ser	synonymous_variant	Exon 5 of 5	ENST00000221315.10	NP_055465.1
ZNF432	NM_001322284.2 link	c.654T>G	p.Ser218Ser	synonymous_variant	Exon 5 of 5		NP_001309213.1
ZNF432	NM_001322285.1 link	c.654T>G	p.Ser218Ser	synonymous_variant	Exon 5 of 5		NP_001309214.1
ZNF432	XM_024451806.2 link	c.366T>G	p.Ser122Ser	synonymous_variant	Exon 2 of 2		XP_024307574.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
ZNF432	ENST00000221315.10 link	c.654T>G	p.Ser218Ser	synonymous_variant	Exon 5 of 5	1	NM_014650.4	ENSP00000221315.4
ZNF432	ENST00000594154.5 link	c.654T>G	p.Ser218Ser	synonymous_variant	Exon 5 of 5	1		ENSP00000470488.1
ZNF432	ENST00000600368.5 link	c.*117T>G		downstream_gene_variant		5		ENSP00000471172.1

Frequencies

GnomAD3 genomes

AF:

0.0474

AC:

7205

AN:

151976

Hom.:

256

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0946

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.0311

Gnomad ASJ

AF:

0.0831

Gnomad EAS

AF:

0.00291

Gnomad SAS

AF:

0.0154

Gnomad FIN

AF:

0.0684

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0238

Gnomad OTH

AF:

0.0408

GnomAD2 exomes

AF:

0.0313

AC:

7857

AN:

251328

AF XY:

0.0299

show subpopulations

Gnomad AFR exome

AF:

0.0963

Gnomad AMR exome

AF:

0.0188

Gnomad ASJ exome

AF:

0.0831

Gnomad EAS exome

AF:

0.00109

Gnomad FIN exome

AF:

0.0614

Gnomad NFE exome

AF:

0.0243

Gnomad OTH exome

AF:

0.0329

GnomAD4 exome

AF:

0.0258

AC:

37658

AN:

1461836

Hom.:

699

Cov.:

AF XY:

0.0254

AC XY:

18493

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.0962

AC:

3222

AN:

33480

American (AMR)

AF:

0.0197

AC:

882

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0841

AC:

2198

AN:

26132

East Asian (EAS)

AF:

0.000403

AC:

AN:

39690

South Asian (SAS)

AF:

0.0171

AC:

1476

AN:

86250

European-Finnish (FIN)

AF:

0.0604

AC:

3226

AN:

53408

Middle Eastern (MID)

AF:

0.0196

AC:

113

AN:

5766

European-Non Finnish (NFE)

AF:

0.0221

AC:

24584

AN:

1111994

Other (OTH)

AF:

0.0321

AC:

1941

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

2311

4623

6934

9246

11557

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

992

1984

2976

3968

4960

<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:

0.0475

AC:

7225

AN:

152094

Hom.:

257

Cov.:

AF XY:

0.0481

AC XY:

3578

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.0948

AC:

3933

AN:

41490

American (AMR)

AF:

0.0310

AC:

474

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0831

AC:

288

AN:

3466

East Asian (EAS)

AF:

0.00272

AC:

AN:

5140

South Asian (SAS)

AF:

0.0156

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.0684

AC:

724

AN:

10590

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0238

AC:

1618

AN:

67996

Other (OTH)

AF:

0.0423

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

362

724

1086

1448

1810

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<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:

0.0315

Hom.:

255

Bravo

AF:

0.0468

Asia WGS

AF:

0.0320

AC:

112

AN:

3478

EpiCase

AF:

0.0242

EpiControl

AF:

0.0260

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

5.9

(source)

DANN

Benign

0.54

PhyloP100

-2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over