dbSNP rs935707: ZNF568:p.Arg377His (chr19-36996821-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001204838.2(ZNF568):c.1130G>A(p.Arg377His) 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 1,550,290 control chromosomes in the GnomAD database, including 216,859 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/13 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 0.54 ( 22261 hom., cov: 31)

Exomes 𝑓: 0.52 ( 194598 hom. )

Consequence

ZNF568
NM_001204838.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.94

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.981675E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
ZNF568	NM_001204838.2 link	c.1130G>A	p.Arg377His	missense_variant	Exon 10 of 10	NP_001191767.1	Q3ZCX4C9JLX5Q96AZ9
ZNF568	NM_001204839.2 link	c.938G>A	p.Arg313His	missense_variant	Exon 9 of 9	NP_001191768.1	Q3ZCX4-3Q96AZ9
ZNF568	XM_017026772.2 link	c.1130G>A	p.Arg377His	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.1130G>A	p.Arg377His	missense_variant	Exon 12 of 12			ENSP00000516244.1		C9JLX5

Frequencies

GnomAD3 genomes

AF:

0.537

AC:

81173

AN:

151052

Hom.:

22227

Cov.:

show subpopulations

Gnomad AFR

AF:

0.617

Gnomad AMI

AF:

0.266

Gnomad AMR

AF:

0.528

Gnomad ASJ

AF:

0.451

Gnomad EAS

AF:

0.273

Gnomad SAS

AF:

0.565

Gnomad FIN

AF:

0.516

Gnomad MID

AF:

0.557

Gnomad NFE

AF:

0.520

Gnomad OTH

AF:

0.541

GnomAD3 exomes

AF:

0.502

AC:

82628

AN:

164688

Hom.:

21178

AF XY:

0.505

AC XY:

44713

AN XY:

88532

show subpopulations

Gnomad AFR exome

AF:

0.619

Gnomad AMR exome

AF:

0.483

Gnomad ASJ exome

AF:

0.443

Gnomad EAS exome

AF:

0.267

Gnomad SAS exome

AF:

0.559

Gnomad FIN exome

AF:

0.511

Gnomad NFE exome

AF:

0.522

Gnomad OTH exome

AF:

0.510

GnomAD4 exome

AF:

0.525

AC:

734457

AN:

1399114

Hom.:

194598

Cov.:

AF XY:

0.525

AC XY:

363254

AN XY:

691600

show subpopulations

Gnomad4 AFR exome

AF:

0.613

Gnomad4 AMR exome

AF:

0.491

Gnomad4 ASJ exome

AF:

0.448

Gnomad4 EAS exome

AF:

0.290

Gnomad4 SAS exome

AF:

0.557

Gnomad4 FIN exome

AF:

0.507

Gnomad4 NFE exome

AF:

0.532

Gnomad4 OTH exome

AF:

0.519

GnomAD4 genome

AF:

0.538

AC:

81268

AN:

151176

Hom.:

22261

Cov.:

AF XY:

0.537

AC XY:

39645

AN XY:

73854

show subpopulations

Gnomad4 AFR

AF:

0.617

Gnomad4 AMR

AF:

0.528

Gnomad4 ASJ

AF:

0.451

Gnomad4 EAS

AF:

0.273

Gnomad4 SAS

AF:

0.564

Gnomad4 FIN

AF:

0.516

Gnomad4 NFE

AF:

0.520

Gnomad4 OTH

AF:

0.540

Alfa

AF:

0.503

Hom.:

24194

Bravo

AF:

0.536

TwinsUK

AF:

0.535

AC:

1982

ALSPAC

AF:

0.553

AC:

2132

ExAC

AF:

0.440

AC:

49274

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

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.046

DANN

Benign

0.87

DEOGEN2

Benign

0.0096

T;.;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0039

LIST_S2

Benign

0.066

T;T;T;T

MetaRNN

Benign

0.0000090

T;T;T;T

MetaSVM

Benign

-0.94

PROVEAN

Benign

-0.25

N;N;.;N

REVEL

Benign

0.016

Sift

Benign

0.60

T;T;.;T

Sift4G

Benign

0.40

T;T;T;T

Vest4

0.014, 0.015

ClinPred

0.011

GERP RS

-3.1

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