dbSNP rs3746414: ZFP64:p.Ser451Asn (chr20-52152840-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_018197.3(ZFP64):c.1352G>A(p.Ser451Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 1,614,018 control chromosomes in the GnomAD database, including 37,715 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 3227 hom., cov: 33)

Exomes 𝑓: 0.21 ( 34488 hom. )

Consequence

ZFP64
NM_018197.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.09

Publications

23 publications found

Variant links:

Genes affected

ZFP64 (HGNC:15940): (ZFP64 zinc finger protein) Predicted to enable DNA binding activity and metal ion binding activity. Predicted to be involved in positive regulation of cytokine production and positive regulation of transcription by RNA polymerase II. Predicted to act upstream of or within positive regulation of mRNA splicing, via spliceosome. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZFP64 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0025477111).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP64	NM_018197.3 link	c.1352G>A	p.Ser451Asn	missense_variant	Exon 6 of 6	ENST00000216923.5	NP_060667.2	Q9NTW7-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP64	ENST00000216923.5 link	c.1352G>A	p.Ser451Asn	missense_variant	Exon 6 of 6	1	NM_018197.3	ENSP00000216923.4		Q9NTW7-5

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

30281

AN:

152086

Hom.:

3223

Cov.:

show subpopulations

Gnomad AFR

AF:

0.152

Gnomad AMI

AF:

0.117

Gnomad AMR

AF:

0.261

Gnomad ASJ

AF:

0.177

Gnomad EAS

AF:

0.0839

Gnomad SAS

AF:

0.185

Gnomad FIN

AF:

0.301

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.211

Gnomad OTH

AF:

0.189

GnomAD2 exomes

AF:

0.221

AC:

55411

AN:

250664

AF XY:

0.216

show subpopulations

Gnomad AFR exome

AF:

0.155

Gnomad AMR exome

AF:

0.351

Gnomad ASJ exome

AF:

0.184

Gnomad EAS exome

AF:

0.0806

Gnomad FIN exome

AF:

0.308

Gnomad NFE exome

AF:

0.213

Gnomad OTH exome

AF:

0.210

GnomAD4 exome

AF:

0.213

AC:

310944

AN:

1461814

Hom.:

34488

Cov.:

AF XY:

0.212

AC XY:

153964

AN XY:

727202

show subpopulations

African (AFR)

AF:

0.154

AC:

5145

AN:

33478

American (AMR)

AF:

0.340

AC:

15187

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.179

AC:

4682

AN:

26132

East Asian (EAS)

AF:

0.110

AC:

4363

AN:

39698

South Asian (SAS)

AF:

0.182

AC:

15695

AN:

86258

European-Finnish (FIN)

AF:

0.309

AC:

16504

AN:

53364

Middle Eastern (MID)

AF:

0.117

AC:

675

AN:

5768

European-Non Finnish (NFE)

AF:

0.213

AC:

237014

AN:

1111998

Other (OTH)

AF:

0.193

AC:

11679

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

16530

33059

49589

66118

82648

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8188

16376

24564

32752

40940

<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:

0.199

AC:

30316

AN:

152204

Hom.:

3227

Cov.:

AF XY:

0.204

AC XY:

15194

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.152

AC:

6313

AN:

41560

American (AMR)

AF:

0.261

AC:

3992

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.177

AC:

613

AN:

3464

East Asian (EAS)

AF:

0.0841

AC:

435

AN:

5170

South Asian (SAS)

AF:

0.185

AC:

894

AN:

4828

European-Finnish (FIN)

AF:

0.301

AC:

3181

AN:

10584

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.211

AC:

14341

AN:

67994

Other (OTH)

AF:

0.189

AC:

400

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1217

2434

3650

4867

6084

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

330

660

990

1320

1650

<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:

0.202

Hom.:

14255

Bravo

AF:

0.196

TwinsUK

AF:

0.204

AC:

757

ALSPAC

AF:

0.196

AC:

756

ESP6500AA

AF:

0.153

AC:

675

ESP6500EA

AF:

0.217

AC:

1863

ExAC

AF:

0.217

AC:

26317

Asia WGS

AF:

0.138

AC:

480

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.0030

(source)

DANN

Benign

0.73

DEOGEN2

Benign

0.017

.;.;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.48

T;T;T

MetaRNN

Benign

0.0025

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.34

.;.;N

PhyloP100

-4.1

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.40

N;N;N

REVEL

Benign

0.12

Sift

Benign

0.85

T;T;T

Sift4G

Benign

0.86

T;T;T

Polyphen

0.0010

B;.;B

Vest4

0.033

MPC

0.55

ClinPred

0.0099

GERP RS

-11

Varity_R

0.026

gMVP

0.14

Mutation Taster

=99/1

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

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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