rs16971886

Positions:

• chr19-36997073-G-A
• chr19-36997073-G-T

Variant summary

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

The ENST00000444991.6(ZNF568):​c.1382G>A​(p.Arg461His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 1,566,038 control chromosomes in the GnomAD database, including 101,825 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/13 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 0.33 (8619 hom., cov: 31)
  • Exomes 𝑓: 0.36 (93206 hom.)
• Consequence: ZNF568 ENST00000444991.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71

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=9.742677E-4).
• 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	UniProt
ZNF568	NM_001204838.2	c.1382G>A	p.Arg461His	missense_variant	10/10
ZNF568	NM_001204839.2	c.1190G>A	p.Arg397His	missense_variant	9/9
ZNF568	XM_017026772.2	c.1382G>A	p.Arg461His	missense_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF568	ENST00000444991.6	c.1382G>A	p.Arg461His	missense_variant	10/10	1
ZNF568	ENST00000591887.1	n.1551G>A		non_coding_transcript_exon_variant	2/2	1
ZNF568	ENST00000455427.7	c.1190G>A	p.Arg397His	missense_variant	9/9	2

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50409 AN: 151608 Hom.: 8604 Cov.: 31

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.0958

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.329

GnomAD3 exomes AF: 0.325 AC: 59579 AN: 183170 Hom.: 10050 AF XY: 0.327 AC XY: 32354 AN XY: 98968

Gnomad AFR exome AF: 0.320

Gnomad AMR exome AF: 0.335

Gnomad ASJ exome AF: 0.275

Gnomad EAS exome AF: 0.0946

Gnomad SAS exome AF: 0.320

Gnomad FIN exome AF: 0.342

Gnomad NFE exome AF: 0.365

Gnomad OTH exome AF: 0.344

GnomAD4 exome AF: 0.358 AC: 506841 AN: 1414314 Hom.: 93206 Cov.: 66 AF XY: 0.357 AC XY: 250157 AN XY: 700520

Gnomad4 AFR exome AF: 0.312

Gnomad4 AMR exome AF: 0.339

Gnomad4 ASJ exome AF: 0.274

Gnomad4 EAS exome AF: 0.105

Gnomad4 SAS exome AF: 0.317

Gnomad4 FIN exome AF: 0.341

Gnomad4 NFE exome AF: 0.376

Gnomad4 OTH exome AF: 0.345

GnomAD4 genome AF: 0.333 AC: 50474 AN: 151724 Hom.: 8619 Cov.: 31 AF XY: 0.332 AC XY: 24570 AN XY: 74106

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.0960

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.329

Alfa AF: 0.341 Hom.: 10966

Bravo AF: 0.332

TwinsUK AF: 0.370 AC: 1371

ALSPAC AF: 0.386 AC: 1486

ExAC AF: 0.279 AC: 32712

Asia WGS AF: 0.232 AC: 805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.045	T;.;.;.
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.54	T;T;T;T
MetaRNN	Benign	0.00097	T;T;T;T
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	1.0	P
PROVEAN	Uncertain	-2.4	N;D;.;D
REVEL	Benign	0.055
Sift	Benign	0.064	T;D;.;D
Sift4G	Benign	0.10	T;T;T;T
Vest4		0.12, 0.060
ClinPred		0.032	T
GERP RS		0.10

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16971886; hg19: chr19-37487975; COSMIC: COSV71278445; COSMIC: COSV71278445;