19-36997579-G-C

Variant names:

• chr19-36997579-G-C
• rs1363753
• ENST00000444991.6:c.1888G>C

Variant summary

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

The ENST00000444991.6(ZNF568):​c.1888G>C​(p.Gly630Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 1,567,882 control chromosomes in the GnomAD database, including 236,438 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 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 0.57 (25471 hom., cov: 31)
  • Exomes 𝑓: 0.54 (210967 hom.)
• Consequence: ZNF568 ENST00000444991.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.15
• 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=2.0722077E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF568	NM_001204838.2	c.1888G>C	p.Gly630Arg	missense_variant	Exon 10 of 10		NP_001191767.1
ZNF568	NM_001204839.2	c.1696G>C	p.Gly566Arg	missense_variant	Exon 9 of 9		NP_001191768.1
ZNF568	XM_017026772.2	c.1888G>C	p.Gly630Arg	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.1888G>C	p.Gly630Arg	missense_variant	Exon 12 of 12			ENSP00000516244.1

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86395 AN: 151456 Hom.: 25429 Cov.: 31

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.560

GnomAD2 exomes AF: 0.564 AC: 110298 AN: 195434 AF XY: 0.564

Gnomad AFR exome AF: 0.732

Gnomad AMR exome AF: 0.579

Gnomad ASJ exome AF: 0.463

Gnomad EAS exome AF: 0.358

Gnomad FIN exome AF: 0.601

Gnomad NFE exome AF: 0.567

Gnomad OTH exome AF: 0.554

GnomAD4 exome AF: 0.543 AC: 768592 AN: 1416310 Hom.: 210967 Cov.: 39 AF XY: 0.543 AC XY: 381486 AN XY: 702730

African (AFR) AF: 0.700 AC: 22856 AN: 32650

American (AMR) AF: 0.580 AC: 22881 AN: 39478

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 11693 AN: 25570

East Asian (EAS) AF: 0.334 AC: 12523 AN: 37536

South Asian (SAS) AF: 0.572 AC: 47411 AN: 82828

European-Finnish (FIN) AF: 0.558 AC: 23806 AN: 42650

Middle Eastern (MID) AF: 0.559 AC: 3188 AN: 5706

European-Non Finnish (NFE) AF: 0.543 AC: 592316 AN: 1090742

Other (OTH) AF: 0.540 AC: 31918 AN: 59150

GnomAD4 genome AF: 0.571 AC: 86500 AN: 151572 Hom.: 25471 Cov.: 31 AF XY: 0.570 AC XY: 42191 AN XY: 74026

African (AFR) AF: 0.698 AC: 28854 AN: 41314

American (AMR) AF: 0.575 AC: 8764 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1575 AN: 3462

East Asian (EAS) AF: 0.314 AC: 1613 AN: 5142

South Asian (SAS) AF: 0.569 AC: 2738 AN: 4810

European-Finnish (FIN) AF: 0.542 AC: 5689 AN: 10494

Middle Eastern (MID) AF: 0.545 AC: 159 AN: 292

European-Non Finnish (NFE) AF: 0.526 AC: 35689 AN: 67804

Other (OTH) AF: 0.560 AC: 1179 AN: 2106

Alfa AF: 0.455 Hom.: 2285

Bravo AF: 0.577

TwinsUK AF: 0.544 AC: 2019

ALSPAC AF: 0.562 AC: 2165

ExAC AF: 0.515 AC: 60571

Asia WGS AF: 0.500 AC: 1741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.027
DANN	Benign	0.21
DEOGEN2	Benign	0.0	.;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.00061	N
LIST_S2	Benign	0.15	T;T
MetaRNN	Benign	0.0000021	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;.
PhyloP100		-5.2
PROVEAN	Benign	2.6	N;.
REVEL	Benign	0.059
Sift	Benign	0.90	T;.
Sift4G	Benign	0.67	T;T
Vest4		0.053
ClinPred		0.0057	T
GERP RS		1.6
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: rs1363753; hg19: chr19-37488481; COSMIC: COSV71278459; COSMIC: COSV71278459;