rs16971886

Variant names:

• chr19-36997073-G-A
• rs16971886
• ENST00000444991.6:c.1382G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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. 10/16 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
• Publications: 21 publications found

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]

ENSG00000291239 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZNF568	NM_001204838.2	c.1382G>A	p.Arg461His	missense_variant	Exon 10 of 10		NP_001191767.1
ZNF568	NM_001204839.2	c.1190G>A	p.Arg397His	missense_variant	Exon 9 of 9		NP_001191768.1
ZNF568	XM_017026772.2	c.1382G>A	p.Arg461His	missense_variant	Exon 10 of 10		XP_016882261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000291239	ENST00000706165.1	c.1382G>A	p.Arg461His	missense_variant	Exon 12 of 12			ENSP00000516244.1

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

GnomAD2 exomes AF: 0.325 AC: 59579 AN: 183170 AF XY: 0.327

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 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

African (AFR) AF: 0.312 AC: 10116 AN: 32416

American (AMR) AF: 0.339 AC: 12975 AN: 38264

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 7003 AN: 25552

East Asian (EAS) AF: 0.105 AC: 3944 AN: 37544

South Asian (SAS) AF: 0.317 AC: 25899 AN: 81762

European-Finnish (FIN) AF: 0.341 AC: 13750 AN: 40372

Middle Eastern (MID) AF: 0.326 AC: 1867 AN: 5732

European-Non Finnish (NFE) AF: 0.376 AC: 410887 AN: 1093512

Other (OTH) AF: 0.345 AC: 20400 AN: 59160

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

African (AFR) AF: 0.321 AC: 13292 AN: 41358

American (AMR) AF: 0.345 AC: 5261 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 934 AN: 3472

East Asian (EAS) AF: 0.0960 AC: 493 AN: 5134

South Asian (SAS) AF: 0.295 AC: 1418 AN: 4800

European-Finnish (FIN) AF: 0.344 AC: 3607 AN: 10494

Middle Eastern (MID) AF: 0.321 AC: 93 AN: 290

European-Non Finnish (NFE) AF: 0.362 AC: 24586 AN: 67904

Other (OTH) AF: 0.329 AC: 693 AN: 2108

Alfa AF: 0.339 Hom.: 16499

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
AlphaMissense	Benign	0.32
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
PhyloP100		-1.7
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
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

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