dbSNP rs1363752: ZNF568:p.Glu569Gly (chr19-36997397-A-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.1706A>G(p.Glu569Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 1,597,698 control chromosomes in the GnomAD database, including 223,664 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 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 0.53 ( 22201 hom., cov: 31)

Exomes 𝑓: 0.53 ( 201463 hom. )

Consequence

ZNF568
ENST00000444991.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.120

Publications

20 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=4.5908264E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
ZNF568	NM_001204838.2 link	c.1706A>G	p.Glu569Gly	missense_variant	Exon 10 of 10	NP_001191767.1	Q3ZCX4C9JLX5Q96AZ9
ZNF568	NM_001204839.2 link	c.1514A>G	p.Glu505Gly	missense_variant	Exon 9 of 9	NP_001191768.1	Q3ZCX4-3Q96AZ9
ZNF568	XM_017026772.2 link	c.1706A>G	p.Glu569Gly	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.1706A>G	p.Glu569Gly	missense_variant	Exon 12 of 12			ENSP00000516244.1		C9JLX5

Frequencies

GnomAD3 genomes

AF:

0.535

AC:

81073

AN:

151644

Hom.:

22167

Cov.:

show subpopulations

Gnomad AFR

AF:

0.615

Gnomad AMI

AF:

0.265

Gnomad AMR

AF:

0.526

Gnomad ASJ

AF:

0.448

Gnomad EAS

AF:

0.266

Gnomad SAS

AF:

0.560

Gnomad FIN

AF:

0.515

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.518

Gnomad OTH

AF:

0.539

GnomAD2 exomes

AF:

0.519

AC:

118367

AN:

228200

AF XY:

0.522

show subpopulations

Gnomad AFR exome

AF:

0.633

Gnomad AMR exome

AF:

0.495

Gnomad ASJ exome

AF:

0.453

Gnomad EAS exome

AF:

0.286

Gnomad FIN exome

AF:

0.546

Gnomad NFE exome

AF:

0.535

Gnomad OTH exome

AF:

0.517

GnomAD4 exome

AF:

0.526

AC:

760519

AN:

1445936

Hom.:

201463

Cov.:

AF XY:

0.527

AC XY:

378640

AN XY:

718918

show subpopulations

African (AFR)

AF:

0.615

AC:

20451

AN:

33276

American (AMR)

AF:

0.499

AC:

21299

AN:

42706

Ashkenazi Jewish (ASJ)

AF:

0.450

AC:

11680

AN:

25962

East Asian (EAS)

AF:

0.293

AC:

11430

AN:

39036

South Asian (SAS)

AF:

0.560

AC:

47816

AN:

85404

European-Finnish (FIN)

AF:

0.522

AC:

24225

AN:

46394

Middle Eastern (MID)

AF:

0.550

AC:

3169

AN:

5764

European-Non Finnish (NFE)

AF:

0.532

AC:

589214

AN:

1107330

Other (OTH)

AF:

0.520

AC:

31235

AN:

60064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

21433

42866

64300

85733

107166

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16910

33820

50730

67640

84550

<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:

0.535

AC:

81168

AN:

151762

Hom.:

22201

Cov.:

AF XY:

0.534

AC XY:

39603

AN XY:

74154

show subpopulations

African (AFR)

AF:

0.615

AC:

25436

AN:

41354

American (AMR)

AF:

0.526

AC:

8024

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.448

AC:

1554

AN:

3466

East Asian (EAS)

AF:

0.266

AC:

1366

AN:

5134

South Asian (SAS)

AF:

0.560

AC:

2680

AN:

4788

European-Finnish (FIN)

AF:

0.515

AC:

5426

AN:

10542

Middle Eastern (MID)

AF:

0.541

AC:

158

AN:

292

European-Non Finnish (NFE)

AF:

0.518

AC:

35149

AN:

67900

Other (OTH)

AF:

0.537

AC:

1134

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1864

3728

5592

7456

9320

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

712

1424

2136

2848

3560

<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:

0.508

Hom.:

3643

Bravo

AF:

0.536

TwinsUK

AF:

0.535

AC:

1982

ALSPAC

AF:

0.553

AC:

2133

ExAC

AF:

0.501

AC:

60512

Asia WGS

AF:

0.457

AC:

1588

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.037

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.26

(source)

DANN

Benign

0.23

DEOGEN2

Benign

0.0037

T;.;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0043

LIST_S2

Benign

0.027

T;T;T

MetaRNN

Benign

0.0000046

T;T;T

MetaSVM

Benign

-0.96

PhyloP100

-0.12

PROVEAN

Benign

5.7

N;N;.

REVEL

Benign

0.020

Sift

Benign

1.0

T;T;.

Sift4G

Benign

1.0

T;T;T

Vest4

0.060, 0.039

ClinPred

0.00087

GERP RS

-0.88

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over