dbSNP rs1667364: ZNF568:p.Ala427Glu (chr19-36996971-C-A) – 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.1280C>A(p.Ala427Glu) 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 1,539,938 control chromosomes in the GnomAD database, including 216,018 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 ( 21998 hom., cov: 31)

Exomes 𝑓: 0.53 ( 194020 hom. )

Consequence

ZNF568
ENST00000444991.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.00

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=3.234077E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
ZNF568	NM_001204838.2 link	c.1280C>A	p.Ala427Glu	missense_variant	Exon 10 of 10	NP_001191767.1	Q3ZCX4C9JLX5Q96AZ9
ZNF568	NM_001204839.2 link	c.1088C>A	p.Ala363Glu	missense_variant	Exon 9 of 9	NP_001191768.1	Q3ZCX4-3Q96AZ9
ZNF568	XM_017026772.2 link	c.1280C>A	p.Ala427Glu	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.1280C>A	p.Ala427Glu	missense_variant	Exon 12 of 12			ENSP00000516244.1		C9JLX5

Frequencies

GnomAD3 genomes

AF:

0.534

AC:

80622

AN:

151108

Hom.:

21963

Cov.:

show subpopulations

Gnomad AFR

AF:

0.614

Gnomad AMI

AF:

0.264

Gnomad AMR

AF:

0.525

Gnomad ASJ

AF:

0.447

Gnomad EAS

AF:

0.264

Gnomad SAS

AF:

0.560

Gnomad FIN

AF:

0.512

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.517

Gnomad OTH

AF:

0.538

GnomAD2 exomes

AF:

0.510

AC:

77368

AN:

151806

AF XY:

0.513

show subpopulations

Gnomad AFR exome

AF:

0.630

Gnomad AMR exome

AF:

0.485

Gnomad ASJ exome

AF:

0.446

Gnomad EAS exome

AF:

0.268

Gnomad FIN exome

AF:

0.522

Gnomad NFE exome

AF:

0.535

Gnomad OTH exome

AF:

0.514

GnomAD4 exome

AF:

0.526

AC:

730193

AN:

1388710

Hom.:

194020

Cov.:

AF XY:

0.526

AC XY:

360951

AN XY:

685894

show subpopulations

African (AFR)

AF:

0.614

AC:

19444

AN:

31684

American (AMR)

AF:

0.493

AC:

17760

AN:

35988

Ashkenazi Jewish (ASJ)

AF:

0.449

AC:

11309

AN:

25196

East Asian (EAS)

AF:

0.291

AC:

10465

AN:

35922

South Asian (SAS)

AF:

0.558

AC:

44380

AN:

79590

European-Finnish (FIN)

AF:

0.512

AC:

18434

AN:

36018

Middle Eastern (MID)

AF:

0.549

AC:

3133

AN:

5702

European-Non Finnish (NFE)

AF:

0.532

AC:

575049

AN:

1080456

Other (OTH)

AF:

0.520

AC:

30219

AN:

58154

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

17977

35954

53932

71909

89886

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16648

33296

49944

66592

83240

<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:

0.534

AC:

80719

AN:

151228

Hom.:

21998

Cov.:

AF XY:

0.533

AC XY:

39379

AN XY:

73862

show subpopulations

African (AFR)

AF:

0.614

AC:

25279

AN:

41166

American (AMR)

AF:

0.525

AC:

7972

AN:

15198

Ashkenazi Jewish (ASJ)

AF:

0.447

AC:

1549

AN:

3462

East Asian (EAS)

AF:

0.265

AC:

1354

AN:

5116

South Asian (SAS)

AF:

0.559

AC:

2671

AN:

4778

European-Finnish (FIN)

AF:

0.512

AC:

5359

AN:

10458

Middle Eastern (MID)

AF:

0.544

AC:

160

AN:

294

European-Non Finnish (NFE)

AF:

0.517

AC:

35007

AN:

67744

Other (OTH)

AF:

0.537

AC:

1127

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1845

3690

5534

7379

9224

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

706

1412

2118

2824

3530

<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:

0.530

Hom.:

18350

Bravo

AF:

0.545

TwinsUK

AF:

0.533

AC:

1976

ALSPAC

AF:

0.554

AC:

2134

ExAC

AF:

0.462

AC:

46460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.32

DEOGEN2

Benign

0.0037

T;.;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.0058

LIST_S2

Benign

0.035

T;T;T;T

MetaRNN

Benign

0.000032

T;T;T;T

MetaSVM

Benign

-0.92

PhyloP100

2.0

PROVEAN

Benign

4.3

N;N;.;N

REVEL

Benign

0.065

Sift

Benign

1.0

T;T;.;T

Sift4G

Benign

1.0

T;T;T;T

Vest4

0.064, 0.050

ClinPred

0.0039

GERP RS

3.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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