dbSNP rs3746414: ZFP64:p.Ser451Asn (chr20-52152840-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -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. 13/19 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

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 made for transcript

Verdict is Benign. Variant got -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

GnomAD3 exomes

AF:

0.221

AC:

55411

AN:

250664

Hom.:

6877

AF XY:

0.216

AC XY:

29288

AN XY:

135532

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 SAS exome

AF:

0.177

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

Gnomad4 AFR exome

AF:

0.154

Gnomad4 AMR exome

AF:

0.340

Gnomad4 ASJ exome

AF:

0.179

Gnomad4 EAS exome

AF:

0.110

Gnomad4 SAS exome

AF:

0.182

Gnomad4 FIN exome

AF:

0.309

Gnomad4 NFE exome

AF:

0.213

Gnomad4 OTH exome

AF:

0.193

GnomAD4 genome

AF:

0.199

AC:

30316

AN:

152204

Hom.:

3227

Cov.:

AF XY:

0.204

AC XY:

15194

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.152

Gnomad4 AMR

AF:

0.261

Gnomad4 ASJ

AF:

0.177

Gnomad4 EAS

AF:

0.0841

Gnomad4 SAS

AF:

0.185

Gnomad4 FIN

AF:

0.301

Gnomad4 NFE

AF:

0.211

Gnomad4 OTH

AF:

0.189

Alfa

AF:

0.201

Hom.:

7912

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

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over