Genetic Variant ZNF568:p.Gly630Cys (chr19-36997579-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000444991.6(ZNF568):c.1888G>T(p.Gly630Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 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 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZNF568
ENST00000444991.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.15

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08205539).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein
ZNF568	NM_001204838.2 link	c.1888G>T	p.Gly630Cys	missense_variant	Exon 10 of 10	NP_001191767.1
ZNF568	NM_001204839.2 link	c.1696G>T	p.Gly566Cys	missense_variant	Exon 9 of 9	NP_001191768.1
ZNF568	XM_017026772.2 link	c.1888G>T	p.Gly630Cys	missense_variant	Exon 10 of 10	XP_016882261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000291239	ENST00000706165.1 link	c.1888G>T	p.Gly630Cys	missense_variant	Exon 12 of 12			ENSP00000516244.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151548

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000512

AC:

AN:

195434

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000115

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000211

AC:

AN:

1422386

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

705442

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32724

American (AMR)

AF:

0.00

AC:

AN:

39498

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25604

East Asian (EAS)

AF:

0.00

AC:

AN:

37568

South Asian (SAS)

AF:

0.0000121

AC:

AN:

82948

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42660

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.00000182

AC:

AN:

1096298

Other (OTH)

AF:

0.00

AC:

AN:

59358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000132

AC:

AN:

151548

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73962

show subpopulations

African (AFR)

AF:

0.0000485

AC:

AN:

41222

American (AMR)

AF:

0.00

AC:

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10508

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67830

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

2285

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.53

(source)

DANN

Benign

0.84

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0081

LIST_S2

Benign

0.11

T;T

M_CAP

Benign

0.0030

MetaRNN

Benign

0.082

T;T

MetaSVM

Benign

-0.93

PhyloP100

-5.2

PROVEAN

Benign

-0.23

N;.

REVEL

Benign

0.028

Sift

Benign

0.17

T;.

Sift4G

Benign

0.089

T;T

Vest4

0.12

MutPred

0.26

Loss of glycosylation at K562 (P = 0.2515);.;

MVP

0.15

ClinPred

0.057

GERP RS

1.6

Mutation Taster

=99/1

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over