Genetic Variant ENST00000444991.6:c.1280C>A (chr19-36996971-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000444991.6(ZNF568):c.1280C>A(p.Ala427Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 1,539,938 control chromosomes in the GnomAD database, including 216,018 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 0.53 ( 21998 hom., cov: 31)

Exomes 𝑓: 0.53 ( 194020 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:

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=3.234077E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
ZNF568	NM_001204838.2 link	c.1280C>A	p.Ala427Glu	missense_variant	Exon 10 of 10	NP_001191767.1	Q3ZCX4C9JLX5Q96AZ9
ZNF568	NM_001204839.2 link	c.1088C>A	p.Ala363Glu	missense_variant	Exon 9 of 9	NP_001191768.1	Q3ZCX4-3Q96AZ9
ZNF568	XM_017026772.2 link	c.1280C>A	p.Ala427Glu	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.1280C>A	p.Ala427Glu	missense_variant	Exon 12 of 12			ENSP00000516244.1		C9JLX5

Frequencies

GnomAD3 genomes

AF:

0.534

AC:

80622

AN:

151108

Hom.:

21963

Cov.:

show subpopulations

Gnomad AFR

AF:

0.614

Gnomad AMI

AF:

0.264

Gnomad AMR

AF:

0.525

Gnomad ASJ

AF:

0.447

Gnomad EAS

AF:

0.264

Gnomad SAS

AF:

0.560

Gnomad FIN

AF:

0.512

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.517

Gnomad OTH

AF:

0.538

GnomAD3 exomes

AF:

0.510

AC:

77368

AN:

151806

Hom.:

20255

AF XY:

0.513

AC XY:

41824

AN XY:

81474

show subpopulations

Gnomad AFR exome

AF:

0.630

Gnomad AMR exome

AF:

0.485

Gnomad ASJ exome

AF:

0.446

Gnomad EAS exome

AF:

0.268

Gnomad SAS exome

AF:

0.561

Gnomad FIN exome

AF:

0.522

Gnomad NFE exome

AF:

0.535

Gnomad OTH exome

AF:

0.514

GnomAD4 exome

AF:

0.526

AC:

730193

AN:

1388710

Hom.:

194020

Cov.:

AF XY:

0.526

AC XY:

360951

AN XY:

685894

show subpopulations

Gnomad4 AFR exome

AF:

0.614

Gnomad4 AMR exome

AF:

0.493

Gnomad4 ASJ exome

AF:

0.449

Gnomad4 EAS exome

AF:

0.291

Gnomad4 SAS exome

AF:

0.558

Gnomad4 FIN exome

AF:

0.512

Gnomad4 NFE exome

AF:

0.532

Gnomad4 OTH exome

AF:

0.520

GnomAD4 genome

AF:

0.534

AC:

80719

AN:

151228

Hom.:

21998

Cov.:

AF XY:

0.533

AC XY:

39379

AN XY:

73862

show subpopulations

Gnomad4 AFR

AF:

0.614

Gnomad4 AMR

AF:

0.525

Gnomad4 ASJ

AF:

0.447

Gnomad4 EAS

AF:

0.265

Gnomad4 SAS

AF:

0.559

Gnomad4 FIN

AF:

0.512

Gnomad4 NFE

AF:

0.517

Gnomad4 OTH

AF:

0.537

Alfa

AF:

0.497

Hom.:

5377

Bravo

AF:

0.545

TwinsUK

AF:

0.533

AC:

1976

ALSPAC

AF:

0.554

AC:

2134

ExAC

AF:

0.462

AC:

46460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.32

DEOGEN2

Benign

0.0037

T;.;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.0058

LIST_S2

Benign

0.035

T;T;T;T

MetaRNN

Benign

0.000032

T;T;T;T

MetaSVM

Benign

-0.92

PROVEAN

Benign

4.3

N;N;.;N

REVEL

Benign

0.065

Sift

Benign

1.0

T;T;.;T

Sift4G

Benign

1.0

T;T;T;T

Vest4

0.064, 0.050

ClinPred

0.0039

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