Variant 19-36997073-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000444991.6(ZNF568):c.1382G>A(p.Arg461His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 1,566,038 control chromosomes in the GnomAD database, including 101,825 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/13 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 0.33 ( 8619 hom., cov: 31)

Exomes 𝑓: 0.36 ( 93206 hom. )

Consequence

ZNF568
ENST00000444991.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.71

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.742677E-4).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein
ZNF568	NM_001204838.2 linkuse as main transcript	c.1382G>A	p.Arg461His	missense_variant	10/10	NP_001191767.1
ZNF568	NM_001204839.2 linkuse as main transcript	c.1190G>A	p.Arg397His	missense_variant	9/9	NP_001191768.1
ZNF568	XM_017026772.2 linkuse as main transcript	c.1382G>A	p.Arg461His	missense_variant	10/10	XP_016882261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
ZNF568	ENST00000444991.6 linkuse as main transcript	c.1382G>A	p.Arg461His	missense_variant	10/10	1	ENSP00000389794
ZNF568	ENST00000591887.1 linkuse as main transcript	n.1551G>A		non_coding_transcript_exon_variant	2/2	1
ZNF568	ENST00000455427.7 linkuse as main transcript	c.1190G>A	p.Arg397His	missense_variant	9/9	2	ENSP00000413396	Q3ZCX4-3

Frequencies

GnomAD3 genomes

AF:

0.332

AC:

50409

AN:

151608

Hom.:

8604

Cov.:

show subpopulations

Gnomad AFR

AF:

0.321

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.344

Gnomad ASJ

AF:

0.269

Gnomad EAS

AF:

0.0958

Gnomad SAS

AF:

0.294

Gnomad FIN

AF:

0.344

Gnomad MID

AF:

0.322

Gnomad NFE

AF:

0.362

Gnomad OTH

AF:

0.329

GnomAD3 exomes

AF:

0.325

AC:

59579

AN:

183170

Hom.:

10050

AF XY:

0.327

AC XY:

32354

AN XY:

98968

show subpopulations

Gnomad AFR exome

AF:

0.320

Gnomad AMR exome

AF:

0.335

Gnomad ASJ exome

AF:

0.275

Gnomad EAS exome

AF:

0.0946

Gnomad SAS exome

AF:

0.320

Gnomad FIN exome

AF:

0.342

Gnomad NFE exome

AF:

0.365

Gnomad OTH exome

AF:

0.344

GnomAD4 exome

AF:

0.358

AC:

506841

AN:

1414314

Hom.:

93206

Cov.:

AF XY:

0.357

AC XY:

250157

AN XY:

700520

show subpopulations

Gnomad4 AFR exome

AF:

0.312

Gnomad4 AMR exome

AF:

0.339

Gnomad4 ASJ exome

AF:

0.274

Gnomad4 EAS exome

AF:

0.105

Gnomad4 SAS exome

AF:

0.317

Gnomad4 FIN exome

AF:

0.341

Gnomad4 NFE exome

AF:

0.376

Gnomad4 OTH exome

AF:

0.345

GnomAD4 genome

AF:

0.333

AC:

50474

AN:

151724

Hom.:

8619

Cov.:

AF XY:

0.332

AC XY:

24570

AN XY:

74106

show subpopulations

Gnomad4 AFR

AF:

0.321

Gnomad4 AMR

AF:

0.345

Gnomad4 ASJ

AF:

0.269

Gnomad4 EAS

AF:

0.0960

Gnomad4 SAS

AF:

0.295

Gnomad4 FIN

AF:

0.344

Gnomad4 NFE

AF:

0.362

Gnomad4 OTH

AF:

0.329

Alfa

AF:

0.341

Hom.:

10966

Bravo

AF:

0.332

TwinsUK

AF:

0.370

AC:

1371

ALSPAC

AF:

0.386

AC:

1486

ExAC

AF:

0.279

AC:

32712

Asia WGS

AF:

0.232

AC:

805

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.045

T;.;.;.

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.54

T;T;T;T

MetaRNN

Benign

0.00097

T;T;T;T

MetaSVM

Benign

-0.91

MutationTaster

Benign

1.0

PROVEAN

Uncertain

-2.4

N;D;.;D

REVEL

Benign

0.055

Sift

Benign

0.064

T;D;.;D

Sift4G

Benign

0.10

T;T;T;T

Vest4

0.12, 0.060

ClinPred

0.032

GERP RS

0.10

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