dbSNP rs1345748: ZNF568:p.Cys535Tyr (chr19-36997295-G-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.1604G>A(p.Cys535Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 1,600,670 control chromosomes in the GnomAD database, including 223,393 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 0.54 ( 22239 hom., cov: 31)

Exomes 𝑓: 0.52 ( 201154 hom. )

Consequence

ZNF568
ENST00000444991.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.329

Publications

21 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=6.838785E-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.1604G>A	p.Cys535Tyr	missense_variant	Exon 10 of 10	NP_001191767.1	Q3ZCX4C9JLX5Q96AZ9
ZNF568	NM_001204839.2 link	c.1412G>A	p.Cys471Tyr	missense_variant	Exon 9 of 9	NP_001191768.1	Q3ZCX4-3Q96AZ9
ZNF568	XM_017026772.2 link	c.1604G>A	p.Cys535Tyr	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.1604G>A	p.Cys535Tyr	missense_variant	Exon 12 of 12			ENSP00000516244.1		C9JLX5

Frequencies

GnomAD3 genomes

AF:

0.535

AC:

81133

AN:

151674

Hom.:

22205

Cov.:

show subpopulations

Gnomad AFR

AF:

0.615

Gnomad AMI

AF:

0.264

Gnomad AMR

AF:

0.526

Gnomad ASJ

AF:

0.447

Gnomad EAS

AF:

0.265

Gnomad SAS

AF:

0.560

Gnomad FIN

AF:

0.516

Gnomad MID

AF:

0.538

Gnomad NFE

AF:

0.518

Gnomad OTH

AF:

0.539

GnomAD2 exomes

AF:

0.509

AC:

117496

AN:

230686

AF XY:

0.512

show subpopulations

Gnomad AFR exome

AF:

0.625

Gnomad AMR exome

AF:

0.487

Gnomad ASJ exome

AF:

0.449

Gnomad EAS exome

AF:

0.277

Gnomad FIN exome

AF:

0.524

Gnomad NFE exome

AF:

0.524

Gnomad OTH exome

AF:

0.516

GnomAD4 exome

AF:

0.525

AC:

760414

AN:

1448876

Hom.:

201154

Cov.:

AF XY:

0.525

AC XY:

378430

AN XY:

720300

show subpopulations

African (AFR)

AF:

0.614

AC:

20414

AN:

33256

American (AMR)

AF:

0.493

AC:

21075

AN:

42736

Ashkenazi Jewish (ASJ)

AF:

0.449

AC:

11675

AN:

25984

East Asian (EAS)

AF:

0.291

AC:

11409

AN:

39148

South Asian (SAS)

AF:

0.559

AC:

47677

AN:

85362

European-Finnish (FIN)

AF:

0.512

AC:

25216

AN:

49208

Middle Eastern (MID)

AF:

0.550

AC:

3169

AN:

5766

European-Non Finnish (NFE)

AF:

0.532

AC:

588558

AN:

1107306

Other (OTH)

AF:

0.519

AC:

31221

AN:

60110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

21993

43986

65978

87971

109964

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16902

33804

50706

67608

84510

<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:

81228

AN:

151794

Hom.:

22239

Cov.:

AF XY:

0.534

AC XY:

39647

AN XY:

74188

show subpopulations

African (AFR)

AF:

0.616

AC:

25479

AN:

41386

American (AMR)

AF:

0.526

AC:

8028

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.447

AC:

1551

AN:

3468

East Asian (EAS)

AF:

0.265

AC:

1362

AN:

5134

South Asian (SAS)

AF:

0.559

AC:

2684

AN:

4802

European-Finnish (FIN)

AF:

0.516

AC:

5423

AN:

10516

Middle Eastern (MID)

AF:

0.544

AC:

160

AN:

294

European-Non Finnish (NFE)

AF:

0.518

AC:

35166

AN:

67904

Other (OTH)

AF:

0.537

AC:

1135

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1887

3773

5660

7546

9433

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:

0.514

Hom.:

3840

Bravo

AF:

0.536

TwinsUK

AF:

0.534

AC:

1981

ALSPAC

AF:

0.553

AC:

2132

ExAC

AF:

0.495

AC:

59846

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

0.063

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.31

(source)

DANN

Benign

0.39

DEOGEN2

Benign

0.0063

T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.024

T;T;T

MetaRNN

Benign

0.0000068

T;T;T

MetaSVM

Benign

-0.94

PhyloP100

-0.33

PROVEAN

Benign

7.3

N;N;.

REVEL

Benign

0.045

Sift

Benign

1.0

T;T;.

Sift4G

Benign

1.0

T;T;T

Vest4

0.087, 0.069

ClinPred

0.0028

GERP RS

3.8

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