chr19-36997397-A-G

Position:

• chr19-36997397-A-G

Variant summary

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

The ENST00000444991.6(ZNF568):​c.1706A>G​(p.Glu569Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 1,597,698 control chromosomes in the GnomAD database, including 223,664 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/13 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 0.53 (22201 hom., cov: 31)
  • Exomes 𝑓: 0.53 (201463 hom.)
• Consequence: ZNF568 ENST00000444991.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120

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=4.5908264E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF568	NM_001204838.2	c.1706A>G	p.Glu569Gly	missense_variant	10/10		NP_001191767.1
ZNF568	NM_001204839.2	c.1514A>G	p.Glu505Gly	missense_variant	9/9		NP_001191768.1
ZNF568	XM_017026772.2	c.1706A>G	p.Glu569Gly	missense_variant	10/10		XP_016882261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF568	ENST00000444991.6	c.1706A>G	p.Glu569Gly	missense_variant	10/10	1		ENSP00000389794
ZNF568	ENST00000591887.1	n.1875A>G		non_coding_transcript_exon_variant	2/2	1
ZNF568	ENST00000455427.7	c.1514A>G	p.Glu505Gly	missense_variant	9/9	2		ENSP00000413396

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81073 AN: 151644 Hom.: 22167 Cov.: 31

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.539

GnomAD3 exomes AF: 0.519 AC: 118367 AN: 228200 Hom.: 30767 AF XY: 0.522 AC XY: 64895 AN XY: 124260

Gnomad AFR exome AF: 0.633

Gnomad AMR exome AF: 0.495

Gnomad ASJ exome AF: 0.453

Gnomad EAS exome AF: 0.286

Gnomad SAS exome AF: 0.569

Gnomad FIN exome AF: 0.546

Gnomad NFE exome AF: 0.535

Gnomad OTH exome AF: 0.517

GnomAD4 exome AF: 0.526 AC: 760519 AN: 1445936 Hom.: 201463 Cov.: 60 AF XY: 0.527 AC XY: 378640 AN XY: 718918

Gnomad4 AFR exome AF: 0.615

Gnomad4 AMR exome AF: 0.499

Gnomad4 ASJ exome AF: 0.450

Gnomad4 EAS exome AF: 0.293

Gnomad4 SAS exome AF: 0.560

Gnomad4 FIN exome AF: 0.522

Gnomad4 NFE exome AF: 0.532

Gnomad4 OTH exome AF: 0.520

GnomAD4 genome AF: 0.535 AC: 81168 AN: 151762 Hom.: 22201 Cov.: 31 AF XY: 0.534 AC XY: 39603 AN XY: 74154

Gnomad4 AFR AF: 0.615

Gnomad4 AMR AF: 0.526

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.560

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.537

Alfa AF: 0.505 Hom.: 3513

Bravo AF: 0.536

TwinsUK AF: 0.535 AC: 1982

ALSPAC AF: 0.553 AC: 2133

ExAC AF: 0.501 AC: 60512

Asia WGS AF: 0.457 AC: 1588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.26
DANN	Benign	0.23
DEOGEN2	Benign	0.0037	T;.;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0043	N
LIST_S2	Benign	0.027	T;T;T
MetaRNN	Benign	0.0000046	T;T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	P
PROVEAN	Benign	5.7	N;N;.
REVEL	Benign	0.020
Sift	Benign	1.0	T;T;.
Sift4G	Benign	1.0	T;T;T
Vest4		0.060, 0.039
ClinPred		0.00087	T
GERP RS		-0.88

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1363752; hg19: chr19-37488299; COSMIC: COSV71278452; COSMIC: COSV71278452;