Genetic Variant ZNF568:p.Tyr488Asp (chr19-36997153-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000444991.6(ZNF568):c.1462T>G(p.Tyr488Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,586,450 control chromosomes in the GnomAD database, including 22,265 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 0.18 ( 2431 hom., cov: 32)

Exomes 𝑓: 0.16 ( 19834 hom. )

Consequence

ZNF568
ENST00000444991.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.62

Publications

16 publications found

Variant links:

Genes affected

ZNF568 (HGNC:25392): (zinc finger protein 568) 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 embryonic placenta morphogenesis and negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF568 links:

ENSG00000291239 (HGNC:):

ENSG00000291239 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=0.0061773956).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
ZNF568	NM_001204838.2 link	c.1462T>G	p.Tyr488Asp	missense_variant	Exon 10 of 10	NP_001191767.1	Q3ZCX4C9JLX5Q96AZ9
ZNF568	NM_001204839.2 link	c.1270T>G	p.Tyr424Asp	missense_variant	Exon 9 of 9	NP_001191768.1	Q3ZCX4-3Q96AZ9
ZNF568	XM_017026772.2 link	c.1462T>G	p.Tyr488Asp	missense_variant	Exon 10 of 10	XP_016882261.1	C9JLX5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000291239	ENST00000706165.1 link	c.1462T>G	p.Tyr488Asp	missense_variant	Exon 12 of 12			ENSP00000516244.1		C9JLX5

Frequencies

GnomAD3 genomes

AF:

0.177

AC:

26840

AN:

151810

Hom.:

2425

Cov.:

show subpopulations

Gnomad AFR

AF:

0.206

Gnomad AMI

AF:

0.157

Gnomad AMR

AF:

0.171

Gnomad ASJ

AF:

0.179

Gnomad EAS

AF:

0.169

Gnomad SAS

AF:

0.263

Gnomad FIN

AF:

0.172

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.189

GnomAD2 exomes

AF:

0.172

AC:

36021

AN:

209504

AF XY:

0.176

show subpopulations

Gnomad AFR exome

AF:

0.204

Gnomad AMR exome

AF:

0.143

Gnomad ASJ exome

AF:

0.170

Gnomad EAS exome

AF:

0.172

Gnomad FIN exome

AF:

0.169

Gnomad NFE exome

AF:

0.158

Gnomad OTH exome

AF:

0.167

GnomAD4 exome

AF:

0.164

AC:

234813

AN:

1434522

Hom.:

19834

Cov.:

AF XY:

0.166

AC XY:

118069

AN XY:

712058

show subpopulations

African (AFR)

AF:

0.209

AC:

6860

AN:

32772

American (AMR)

AF:

0.144

AC:

5856

AN:

40598

Ashkenazi Jewish (ASJ)

AF:

0.174

AC:

4487

AN:

25748

East Asian (EAS)

AF:

0.185

AC:

7090

AN:

38396

South Asian (SAS)

AF:

0.241

AC:

20082

AN:

83432

European-Finnish (FIN)

AF:

0.165

AC:

7827

AN:

47384

Middle Eastern (MID)

AF:

0.221

AC:

1268

AN:

5750

European-Non Finnish (NFE)

AF:

0.156

AC:

171305

AN:

1100774

Other (OTH)

AF:

0.168

AC:

10038

AN:

59668

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

11843

23687

35530

47374

59217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6302

12604

18906

25208

31510

<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:

0.177

AC:

26865

AN:

151928

Hom.:

2431

Cov.:

AF XY:

0.178

AC XY:

13232

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.206

AC:

8537

AN:

41426

American (AMR)

AF:

0.171

AC:

2607

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.179

AC:

620

AN:

3470

East Asian (EAS)

AF:

0.169

AC:

869

AN:

5146

South Asian (SAS)

AF:

0.261

AC:

1253

AN:

4796

European-Finnish (FIN)

AF:

0.172

AC:

1820

AN:

10558

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.155

AC:

10559

AN:

67954

Other (OTH)

AF:

0.188

AC:

396

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1103

2206

3309

4412

5515

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

294

588

882

1176

1470

<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:

0.159

Hom.:

3659

Bravo

AF:

0.175

TwinsUK

AF:

0.166

AC:

614

ALSPAC

AF:

0.168

AC:

647

ExAC

AF:

0.159

AC:

19087

Asia WGS

AF:

0.221

AC:

768

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.34

T;.;.;.

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.90

D;T;T;D

MetaRNN

Benign

0.0062

T;T;T;T

MetaSVM

Benign

-1.1

PhyloP100

7.6

PROVEAN

Pathogenic

-6.4

D;D;.;D

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

D;D;.;D

Sift4G

Pathogenic

0.0

D;D;D;D

Vest4

0.46, 0.47

ClinPred

0.048

GERP RS

3.9

Mutation Taster

=97/3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over