rs1667363

Variant names:

• chr19-36996964-A-T
• rs1667363
• ENST00000444991.6:c.1273A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000444991.6(ZNF568):​c.1273A>T​(p.Ser425Cys) variant causes a missense change. The variant allele was found at a frequency of 0.527 in 1,539,246 control chromosomes in the GnomAD database, including 215,871 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 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 0.53 (22004 hom., cov: 31)
  • Exomes 𝑓: 0.53 (193867 hom.)
• Consequence: ZNF568 ENST00000444991.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.67
• Publications: 16 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=1.8989978E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF568	NM_001204838.2	c.1273A>T	p.Ser425Cys	missense_variant	Exon 10 of 10		NP_001191767.1
ZNF568	NM_001204839.2	c.1081A>T	p.Ser361Cys	missense_variant	Exon 9 of 9		NP_001191768.1
ZNF568	XM_017026772.2	c.1273A>T	p.Ser425Cys	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.1273A>T	p.Ser425Cys	missense_variant	Exon 12 of 12			ENSP00000516244.1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80650 AN: 151264 Hom.: 21969 Cov.: 31

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.538

GnomAD2 exomes AF: 0.509 AC: 76550 AN: 150466 AF XY: 0.513

Gnomad AFR exome AF: 0.629

Gnomad AMR exome AF: 0.485

Gnomad ASJ exome AF: 0.446

Gnomad EAS exome AF: 0.268

Gnomad FIN exome AF: 0.520

Gnomad NFE exome AF: 0.534

Gnomad OTH exome AF: 0.514

GnomAD4 exome AF: 0.526 AC: 729690 AN: 1387862 Hom.: 193867 Cov.: 57 AF XY: 0.526 AC XY: 360669 AN XY: 685438

African (AFR) AF: 0.614 AC: 19435 AN: 31674

American (AMR) AF: 0.493 AC: 17723 AN: 35918

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 11306 AN: 25190

East Asian (EAS) AF: 0.291 AC: 10459 AN: 35894

South Asian (SAS) AF: 0.557 AC: 44336 AN: 79534

European-Finnish (FIN) AF: 0.511 AC: 18317 AN: 35842

Middle Eastern (MID) AF: 0.549 AC: 3133 AN: 5704

European-Non Finnish (NFE) AF: 0.532 AC: 574783 AN: 1079990

Other (OTH) AF: 0.520 AC: 30198 AN: 58116

GnomAD4 genome AF: 0.533 AC: 80747 AN: 151384 Hom.: 22004 Cov.: 31 AF XY: 0.533 AC XY: 39395 AN XY: 73976

African (AFR) AF: 0.614 AC: 25293 AN: 41214

American (AMR) AF: 0.524 AC: 7980 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1547 AN: 3462

East Asian (EAS) AF: 0.264 AC: 1358 AN: 5148

South Asian (SAS) AF: 0.558 AC: 2673 AN: 4792

European-Finnish (FIN) AF: 0.512 AC: 5357 AN: 10468

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.517 AC: 35013 AN: 67782

Other (OTH) AF: 0.537 AC: 1125 AN: 2096

Alfa AF: 0.511 Hom.: 3697

Bravo AF: 0.536

TwinsUK AF: 0.533 AC: 1976

ALSPAC AF: 0.554 AC: 2134

ExAC AF: 0.464 AC: 46611

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
AlphaMissense	Benign	0.016
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	14
DANN	Benign	0.055
DEOGEN2	Benign	0.049	T;.;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.0092	N
LIST_S2	Benign	0.066	T;T;T;T
MetaRNN	Benign	0.000019	T;T;T;T
MetaSVM	Benign	-0.96	T
PhyloP100		4.7
PROVEAN	Benign	9.3	N;N;.;N
REVEL	Benign	0.12
Sift	Benign	1.0	T;T;.;T
Sift4G	Benign	1.0	T;T;T;T
Vest4		0.14, 0.12
ClinPred		0.0033	T
GERP RS		3.7
Mutation Taster		=95/5	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1667363; hg19: chr19-37487866; COSMIC: COSV71278474; COSMIC: COSV71278474;