chr19-36997570-C-G

Position:

• chr19-36997570-C-G

Variant summary

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

The NM_001204838.2(ZNF568):​c.1879C>G​(p.Pro627Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 1,574,466 control chromosomes in the GnomAD database, including 222,477 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 (22112 hom., cov: 31)
  • Exomes 𝑓: 0.53 (200365 hom.)
• Consequence: ZNF568 NM_001204838.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.58

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=3.547529E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF568	NM_001204838.2	c.1879C>G	p.Pro627Ala	missense_variant	10/10		NP_001191767.1
ZNF568	NM_001204839.2	c.1687C>G	p.Pro563Ala	missense_variant	9/9		NP_001191768.1
ZNF568	XM_017026772.2	c.1879C>G	p.Pro627Ala	missense_variant	10/10		XP_016882261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000291239	ENST00000706165.1	c.1879C>G	p.Pro627Ala	missense_variant	12/12			ENSP00000516244.1

Frequencies

GnomAD3 genomes AF: 0.534 AC: 80890 AN: 151446 Hom.: 22078 Cov.: 31

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.538

GnomAD3 exomes AF: 0.535 AC: 108424 AN: 202578 Hom.: 28980 AF XY: 0.540 AC XY: 59314 AN XY: 109916

Gnomad AFR exome AF: 0.655

Gnomad AMR exome AF: 0.504

Gnomad ASJ exome AF: 0.457

Gnomad EAS exome AF: 0.300

Gnomad SAS exome AF: 0.579

Gnomad FIN exome AF: 0.578

Gnomad NFE exome AF: 0.555

Gnomad OTH exome AF: 0.530

GnomAD4 exome AF: 0.528 AC: 751224 AN: 1422902 Hom.: 200365 Cov.: 41 AF XY: 0.529 AC XY: 373611 AN XY: 706374

Gnomad4 AFR exome AF: 0.616

Gnomad4 AMR exome AF: 0.505

Gnomad4 ASJ exome AF: 0.451

Gnomad4 EAS exome AF: 0.297

Gnomad4 SAS exome AF: 0.563

Gnomad4 FIN exome AF: 0.535

Gnomad4 NFE exome AF: 0.533

Gnomad4 OTH exome AF: 0.521

GnomAD4 genome AF: 0.534 AC: 80985 AN: 151564 Hom.: 22112 Cov.: 31 AF XY: 0.534 AC XY: 39506 AN XY: 74034

Gnomad4 AFR AF: 0.614

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.560

Gnomad4 FIN AF: 0.514

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.537

Alfa AF: 0.424 Hom.: 1976

Bravo AF: 0.536

TwinsUK AF: 0.535 AC: 1985

ALSPAC AF: 0.554 AC: 2134

ExAC AF: 0.497 AC: 58827

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
BayesDel_addAF	Benign	-0.87	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.0030
DANN	Benign	0.16
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0067	N
LIST_S2	Benign	0.036	T;T
MetaRNN	Benign	0.0000035	T;T
MetaSVM	Benign	-0.95	T
PROVEAN	Benign	2.6	N;.
REVEL	Benign	0.040
Sift	Benign	1.0	T;.
Sift4G	Benign	1.0	T;T
Vest4		0.030
ClinPred		0.0073	T
GERP RS		-3.9

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1644698; hg19: chr19-37488472; COSMIC: COSV71278458; COSMIC: COSV71278458;