19-36997663-C-G

Position:

• chr19-36997663-C-G

Variant summary

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

The ENST00000444991.6(ZNF568):​c.*64C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,225,206 control chromosomes in the GnomAD database, including 69,370 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 0.33 (8603 hom., cov: 31)
  • Exomes 𝑓: 0.34 (60767 hom.)
• Consequence: ZNF568 ENST00000444991.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96

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 (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF568	NM_001204838.2	c.*64C>G		3_prime_UTR_variant	10/10		NP_001191767.1
ZNF568	NM_001204839.2	c.*64C>G		3_prime_UTR_variant	9/9		NP_001191768.1
ZNF568	XM_017026772.2	c.*64C>G		3_prime_UTR_variant	10/10		XP_016882261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF568	ENST00000444991.6	c.*64C>G		3_prime_UTR_variant	10/10	1		ENSP00000389794
ZNF568	ENST00000591887.1	n.2141C>G		non_coding_transcript_exon_variant	2/2	1
ZNF568	ENST00000433993.6	c.*64C>G		3_prime_UTR_variant	5/5	4		ENSP00000399643

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50375 AN: 151680 Hom.: 8587 Cov.: 31

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.0952

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.328

GnomAD3 exomes AF: 0.325 AC: 45801 AN: 141016 Hom.: 7860 AF XY: 0.325 AC XY: 24729 AN XY: 75978

Gnomad AFR exome AF: 0.320

Gnomad AMR exome AF: 0.333

Gnomad ASJ exome AF: 0.274

Gnomad EAS exome AF: 0.0917

Gnomad SAS exome AF: 0.318

Gnomad FIN exome AF: 0.354

Gnomad NFE exome AF: 0.373

Gnomad OTH exome AF: 0.343

GnomAD4 exome AF: 0.336 AC: 360226 AN: 1073408 Hom.: 60767 Cov.: 15 AF XY: 0.336 AC XY: 182320 AN XY: 542482

Gnomad4 AFR exome AF: 0.304

Gnomad4 AMR exome AF: 0.337

Gnomad4 ASJ exome AF: 0.269

Gnomad4 EAS exome AF: 0.105

Gnomad4 SAS exome AF: 0.314

Gnomad4 FIN exome AF: 0.343

Gnomad4 NFE exome AF: 0.351

Gnomad4 OTH exome AF: 0.328

GnomAD4 genome AF: 0.332 AC: 50442 AN: 151798 Hom.: 8603 Cov.: 31 AF XY: 0.331 AC XY: 24550 AN XY: 74170

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.0955

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.328

Alfa AF: 0.224 Hom.: 724

Bravo AF: 0.332

Asia WGS AF: 0.232 AC: 807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.7
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3745770; hg19: chr19-37488565; COSMIC: COSV71278461; COSMIC: COSV71278461;