Genetic Variant ZNF568:p.Ter636Argext*? (chr19-36997597-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM4BA1

The ENST00000444991.6(ZNF568):c.1906T>C(p.Ter636Argext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 1,549,972 control chromosomes in the GnomAD database, including 219,692 homozygotes. In-silico tool predicts 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 ( 22086 hom., cov: 31)

Exomes 𝑓: 0.53 ( 197606 hom. )

Consequence

ZNF568
ENST00000444991.6 stop_lost

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.79

Publications

19 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: Likely_benign. The variant received -6 ACMG points.

PM4

Stoplost variant in ENST00000444991.6 Downstream stopcodon found after 809 codons.

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.1906T>C	p.Ter636Argext*?	stop_lost	Exon 10 of 10	NP_001191767.1	Q3ZCX4C9JLX5Q96AZ9
ZNF568	NM_001204839.2 link	c.1714T>C	p.Ter572Argext*?	stop_lost	Exon 9 of 9	NP_001191768.1	Q3ZCX4-3Q96AZ9
ZNF568	XM_017026772.2 link	c.1906T>C	p.Ter636Argext*?	stop_lost	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.1906T>C	p.Ter636Argext*?	stop_lost	Exon 12 of 12			ENSP00000516244.1		C9JLX5

Frequencies

GnomAD3 genomes

AF:

0.534

AC:

80827

AN:

151346

Hom.:

22052

Cov.:

show subpopulations

Gnomad AFR

AF:

0.614

Gnomad AMI

AF:

0.262

Gnomad AMR

AF:

0.525

Gnomad ASJ

AF:

0.447

Gnomad EAS

AF:

0.265

Gnomad SAS

AF:

0.559

Gnomad FIN

AF:

0.513

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.517

Gnomad OTH

AF:

0.538

GnomAD2 exomes

AF:

0.538

AC:

96479

AN:

179314

AF XY:

0.542

show subpopulations

Gnomad AFR exome

AF:

0.658

Gnomad AMR exome

AF:

0.501

Gnomad ASJ exome

AF:

0.456

Gnomad EAS exome

AF:

0.295

Gnomad FIN exome

AF:

0.587

Gnomad NFE exome

AF:

0.563

Gnomad OTH exome

AF:

0.534

GnomAD4 exome

AF:

0.528

AC:

737866

AN:

1398508

Hom.:

197606

Cov.:

AF XY:

0.529

AC XY:

366506

AN XY:

693294

show subpopulations

African (AFR)

AF:

0.616

AC:

19797

AN:

32122

American (AMR)

AF:

0.504

AC:

19189

AN:

38044

Ashkenazi Jewish (ASJ)

AF:

0.450

AC:

11412

AN:

25352

East Asian (EAS)

AF:

0.297

AC:

10950

AN:

36836

South Asian (SAS)

AF:

0.562

AC:

45861

AN:

81534

European-Finnish (FIN)

AF:

0.534

AC:

21922

AN:

41058

Middle Eastern (MID)

AF:

0.551

AC:

3124

AN:

5674

European-Non Finnish (NFE)

AF:

0.533

AC:

575151

AN:

1079428

Other (OTH)

AF:

0.521

AC:

30460

AN:

58460

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

15402

30804

46207

61609

77011

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.534

AC:

80922

AN:

151464

Hom.:

22086

Cov.:

AF XY:

0.533

AC XY:

39461

AN XY:

73968

show subpopulations

African (AFR)

AF:

0.614

AC:

25379

AN:

41314

American (AMR)

AF:

0.525

AC:

7990

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.447

AC:

1549

AN:

3462

East Asian (EAS)

AF:

0.266

AC:

1358

AN:

5114

South Asian (SAS)

AF:

0.559

AC:

2679

AN:

4796

European-Finnish (FIN)

AF:

0.513

AC:

5384

AN:

10486

Middle Eastern (MID)

AF:

0.542

AC:

156

AN:

288

European-Non Finnish (NFE)

AF:

0.517

AC:

35061

AN:

67776

Other (OTH)

AF:

0.537

AC:

1129

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1869

3738

5608

7477

9346

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.512

Hom.:

32002

Bravo

AF:

0.536

TwinsUK

AF:

0.535

AC:

1983

ALSPAC

AF:

0.553

AC:

2132

ExAC

AF:

0.498

AC:

57311

Asia WGS

AF:

0.456

AC:

1585

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.87

Eigen

Benign

0.18

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.0017

PhyloP100

-2.8

Vest4

0.0010

GERP RS

2.7

Mutation Taster

=189/11

polymorphism (auto)

(source)

Splicing

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

Publications

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19-36997597-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over