19-36997579-G-C

Position:

• chr19-36997579-G-C

Variant summary

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

The NM_001204838.2(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. 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 0.57 (25471 hom., cov: 31)
  • Exomes 𝑓: 0.54 (210967 hom.)
• Consequence: ZNF568 NM_001204838.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.15

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ZNF568	NM_001204838.2	c.1888G>C	p.Gly630Arg	missense_variant	10/10		NP_001191767.1
ZNF568	NM_001204839.2	c.1696G>C	p.Gly566Arg	missense_variant	9/9		NP_001191768.1
ZNF568	XM_017026772.2	c.1888G>C	p.Gly630Arg	missense_variant	10/10		XP_016882261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000291239	ENST00000706165.1	c.1888G>C	p.Gly630Arg	missense_variant	12/12			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

GnomAD3 exomes AF: 0.564 AC: 110298 AN: 195434 Hom.: 31094 AF XY: 0.564 AC XY: 59793 AN XY: 105930

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 SAS exome AF: 0.590

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

Gnomad4 AFR exome AF: 0.700

Gnomad4 AMR exome AF: 0.580

Gnomad4 ASJ exome AF: 0.457

Gnomad4 EAS exome AF: 0.334

Gnomad4 SAS exome AF: 0.572

Gnomad4 FIN exome AF: 0.558

Gnomad4 NFE exome AF: 0.543

Gnomad4 OTH exome AF: 0.540

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

Gnomad4 AFR AF: 0.698

Gnomad4 AMR AF: 0.575

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.569

Gnomad4 FIN AF: 0.542

Gnomad4 NFE AF: 0.526

Gnomad4 OTH AF: 0.560

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
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.027
DANN	Benign	0.21
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
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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1363753; hg19: chr19-37488481; COSMIC: COSV71278459; COSMIC: COSV71278459;