Variant chr19-36996971-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000444991.6(ZNF568):c.1280C>T(p.Ala427Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0187 in 1,541,896 control chromosomes in the GnomAD database, including 359 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/13 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 0.016 ( 24 hom., cov: 31)

Exomes 𝑓: 0.019 ( 335 hom. )

Consequence

ZNF568
ENST00000444991.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.00

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006697446).

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0158 (2397/151334) while in subpopulation SAS AF= 0.0357 (171/4784). AF 95% confidence interval is 0.0314. There are 24 homozygotes in gnomad4. There are 1198 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons
ZNF568	NM_001204838.2 linkuse as main transcript	c.1280C>T	p.Ala427Val	missense_variant	10/10
ZNF568	NM_001204839.2 linkuse as main transcript	c.1088C>T	p.Ala363Val	missense_variant	9/9
ZNF568	XM_017026772.2 linkuse as main transcript	c.1280C>T	p.Ala427Val	missense_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	UniProt
ZNF568	ENST00000444991.6 linkuse as main transcript	c.1280C>T	p.Ala427Val	missense_variant	10/10	1
ZNF568	ENST00000591887.1 linkuse as main transcript	n.1449C>T		non_coding_transcript_exon_variant	2/2	1
ZNF568	ENST00000455427.7 linkuse as main transcript	c.1088C>T	p.Ala363Val	missense_variant	9/9	2	Q3ZCX4-3

Frequencies

GnomAD3 genomes

AF:

0.0159

AC:

2400

AN:

151214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0184

Gnomad ASJ

AF:

0.0300

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.0357

Gnomad FIN

AF:

0.00487

Gnomad MID

AF:

0.0350

Gnomad NFE

AF:

0.0171

Gnomad OTH

AF:

0.0250

GnomAD3 exomes

AF:

0.0198

AC:

3013

AN:

151806

Hom.:

AF XY:

0.0217

AC XY:

1771

AN XY:

81474

show subpopulations

Gnomad AFR exome

AF:

0.0139

Gnomad AMR exome

AF:

0.0160

Gnomad ASJ exome

AF:

0.0367

Gnomad EAS exome

AF:

0.000356

Gnomad SAS exome

AF:

0.0397

Gnomad FIN exome

AF:

0.00524

Gnomad NFE exome

AF:

0.0176

Gnomad OTH exome

AF:

0.0235

GnomAD4 exome

AF:

0.0191

AC:

26500

AN:

1390562

Hom.:

335

Cov.:

AF XY:

0.0199

AC XY:

13669

AN XY:

686746

show subpopulations

Gnomad4 AFR exome

AF:

0.0137

Gnomad4 AMR exome

AF:

0.0162

Gnomad4 ASJ exome

AF:

0.0349

Gnomad4 EAS exome

AF:

0.000195

Gnomad4 SAS exome

AF:

0.0401

Gnomad4 FIN exome

AF:

0.00694

Gnomad4 NFE exome

AF:

0.0182

Gnomad4 OTH exome

AF:

0.0210

GnomAD4 genome

AF:

0.0158

AC:

2397

AN:

151334

Hom.:

Cov.:

AF XY:

0.0162

AC XY:

1198

AN XY:

73916

show subpopulations

Gnomad4 AFR

AF:

0.0138

Gnomad4 AMR

AF:

0.0183

Gnomad4 ASJ

AF:

0.0300

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.0357

Gnomad4 FIN

AF:

0.00487

Gnomad4 NFE

AF:

0.0172

Gnomad4 OTH

AF:

0.0242

Alfa

AF:

0.00784

Hom.:

5377

TwinsUK

AF:

0.0216

AC:

ALSPAC

AF:

0.0179

AC:

ExAC

AF:

0.0122

AC:

1229

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0070

T;.;.;.

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.19

T;T;T;T

MetaRNN

Benign

0.0067

T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

PROVEAN

Benign

-0.63

N;N;.;N

REVEL

Benign

0.069

Sift

Benign

0.17

T;T;.;D

Sift4G

Benign

0.15

T;T;T;D

Vest4

0.083, 0.062

ClinPred

0.0069

GERP RS

3.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over