chr19-36991249-A-G

Position:

• chr19-36991249-A-G

Variant summary

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

The ENST00000444991.6(ZNF568):​c.479A>G​(p.Asp160Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 1,534,716 control chromosomes in the GnomAD database, including 225,748 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 0.56 (24509 hom., cov: 32)
  • Exomes 𝑓: 0.54 (201239 hom.)
• Consequence: ZNF568 ENST00000444991.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316

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=8.637041E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF568	NM_001204838.2	c.479A>G	p.Asp160Gly	missense_variant	8/10		NP_001191767.1
ZNF568	NM_001204839.2	c.287A>G	p.Asp96Gly	missense_variant	7/9		NP_001191768.1
ZNF568	XM_017026772.2	c.479A>G	p.Asp160Gly	missense_variant	8/10		XP_016882261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF568	ENST00000444991.6	c.479A>G	p.Asp160Gly	missense_variant	8/10	1		ENSP00000389794
ZNF568	ENST00000591887.1	n.197A>G		non_coding_transcript_exon_variant	1/2	1
ZNF568	ENST00000455427.7	c.287A>G	p.Asp96Gly	missense_variant	7/9	2		ENSP00000413396

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84876 AN: 151902 Hom.: 24471 Cov.: 32

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.552

GnomAD3 exomes AF: 0.510 AC: 70413 AN: 138030 Hom.: 18553 AF XY: 0.514 AC XY: 38348 AN XY: 74658

Gnomad AFR exome AF: 0.673

Gnomad AMR exome AF: 0.487

Gnomad ASJ exome AF: 0.457

Gnomad EAS exome AF: 0.262

Gnomad SAS exome AF: 0.567

Gnomad FIN exome AF: 0.523

Gnomad NFE exome AF: 0.530

Gnomad OTH exome AF: 0.520

GnomAD4 exome AF: 0.537 AC: 741934 AN: 1382696 Hom.: 201239 Cov.: 40 AF XY: 0.537 AC XY: 366201 AN XY: 682232

Gnomad4 AFR exome AF: 0.676

Gnomad4 AMR exome AF: 0.498

Gnomad4 ASJ exome AF: 0.462

Gnomad4 EAS exome AF: 0.289

Gnomad4 SAS exome AF: 0.567

Gnomad4 FIN exome AF: 0.530

Gnomad4 NFE exome AF: 0.542

Gnomad4 OTH exome AF: 0.532

GnomAD4 genome AF: 0.559 AC: 84975 AN: 152020 Hom.: 24509 Cov.: 32 AF XY: 0.558 AC XY: 41464 AN XY: 74310

Gnomad4 AFR AF: 0.673

Gnomad4 AMR AF: 0.536

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.264

Gnomad4 SAS AF: 0.571

Gnomad4 FIN AF: 0.546

Gnomad4 NFE AF: 0.527

Gnomad4 OTH AF: 0.550

Alfa AF: 0.517 Hom.: 32666

Bravo AF: 0.560

TwinsUK AF: 0.543 AC: 2012

ALSPAC AF: 0.562 AC: 2166

ExAC AF: 0.494 AC: 9608

Asia WGS AF: 0.468 AC: 1629 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.014	T;.;.;.
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.18	T;T;T;T
MetaRNN	Benign	0.0000086	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P
PROVEAN	Benign	-2.2	N;N;.;D
REVEL	Benign	0.051
Sift	Benign	0.20	T;T;.;D
Sift4G	Benign	0.15	T;T;T;D
Vest4		0.10, 0.048
ClinPred		0.0037	T
GERP RS		2.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1667354; hg19: chr19-37482151; COSMIC: COSV71278669; COSMIC: COSV71278669;