rs1345748

chr19-36997295-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000444991.6(ZNF568):c.1604G>A(p.Cys535Tyr) 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 1,600,670 control chromosomes in the GnomAD database, including 223,393 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 (22239 hom., cov: 31)
  • Exomes 𝑓: 0.52 (201154 hom.)
• Consequence: ZNF568 ENST00000444991.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.838785E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF568	NM_001204838.2	c.1604G>A	p.Cys535Tyr	missense_variant	10/10
ZNF568	NM_001204839.2	c.1412G>A	p.Cys471Tyr	missense_variant	9/9
ZNF568	XM_017026772.2	c.1604G>A	p.Cys535Tyr	missense_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF568	ENST00000444991.6	c.1604G>A	p.Cys535Tyr	missense_variant	10/10	1
ZNF568	ENST00000591887.1	n.1773G>A		non_coding_transcript_exon_variant	2/2	1
ZNF568	ENST00000455427.7	c.1412G>A	p.Cys471Tyr	missense_variant	9/9	2

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81133 AN: 151674 Hom.: 22205 Cov.: 31

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.539

GnomAD3 exomes AF: 0.509 AC: 117496 AN: 230686 Hom.: 30179 AF XY: 0.512 AC XY: 64256 AN XY: 125392

Gnomad AFR exome AF: 0.625

Gnomad AMR exome AF: 0.487

Gnomad ASJ exome AF: 0.449

Gnomad EAS exome AF: 0.277

Gnomad SAS exome AF: 0.565

Gnomad FIN exome AF: 0.524

Gnomad NFE exome AF: 0.524

Gnomad OTH exome AF: 0.516

GnomAD4 exome AF: 0.525 AC: 760414 AN: 1448876 Hom.: 201154 Cov.: 62 AF XY: 0.525 AC XY: 378430 AN XY: 720300

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: 0.559

Gnomad4 FIN exome AF: 0.512

Gnomad4 NFE exome AF: 0.532

Gnomad4 OTH exome AF: 0.519

GnomAD4 genome AF: 0.535 AC: 81228 AN: 151794 Hom.: 22239 Cov.: 31 AF XY: 0.534 AC XY: 39647 AN XY: 74188

Gnomad4 AFR AF: 0.616

Gnomad4 AMR AF: 0.526

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.516

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.537

Alfa AF: 0.512 Hom.: 3710

Bravo AF: 0.536

TwinsUK AF: 0.534 AC: 1981

ALSPAC AF: 0.553 AC: 2132

ExAC AF: 0.495 AC: 59846

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	-0.80	T
BayesDel_noAF	Benign	-0.78
Cadd	Benign	0.31
Dann	Benign	0.39
DEOGEN2	Benign	0.0063	T;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.024	T;T;T
MetaRNN	Benign	0.0000068	T;T;T
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	1.0	P
PROVEAN	Benign	7.3	N;N;.
REVEL	Benign	0.045
Sift	Benign	1.0	T;T;.
Sift4G	Benign	1.0	T;T;T
Vest4		0.087, 0.069
ClinPred		0.0028	T
GERP RS		3.8

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1345748; hg19: chr19-37488197; COSMIC: COSV71278430; COSMIC: COSV71278430;