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

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM4BA1

The NM_001204838.2(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
NM_001204838.2 stop_lost

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.79

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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM4

Stoplost variant in NM_001204838.2 Downstream stopcodon found after 806 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

GnomAD3 exomes

AF:

0.538

AC:

96479

AN:

179314

Hom.:

26303

AF XY:

0.542

AC XY:

52569

AN XY:

96934

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 SAS exome

AF:

0.578

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

Gnomad4 AFR exome

AF:

0.616

Gnomad4 AMR exome

AF:

0.504

Gnomad4 ASJ exome

AF:

0.450

Gnomad4 EAS exome

AF:

0.297

Gnomad4 SAS exome

AF:

0.562

Gnomad4 FIN exome

AF:

0.534

Gnomad4 NFE exome

AF:

0.533

Gnomad4 OTH exome

AF:

0.521

GnomAD4 genome

AF:

0.534

AC:

80922

AN:

151464

Hom.:

22086

Cov.:

AF XY:

0.533

AC XY:

39461

AN XY:

73968

show subpopulations

Gnomad4 AFR

AF:

0.614

Gnomad4 AMR

AF:

0.525

Gnomad4 ASJ

AF:

0.447

Gnomad4 EAS

AF:

0.266

Gnomad4 SAS

AF:

0.559

Gnomad4 FIN

AF:

0.513

Gnomad4 NFE

AF:

0.517

Gnomad4 OTH

AF:

0.537

Alfa

AF:

0.501

Hom.:

22771

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

DANN

Benign

0.87

Eigen

Benign

0.18

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.0017

Vest4

0.0010

GERP RS

2.7

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