19-36449858-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001145344.1(ZNF566):c.376C>A(p.Arg126=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 1,613,476 control chromosomes in the GnomAD database, including 263,797 homozygotes. In-silico tool predicts 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 (25078 hom., cov: 32)
  • Exomes 𝑓: 0.57 (238719 hom.)
• Consequence: ZNF566 NM_001145344.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14

Genes affected

ZNF566 (HGNC:25919): (zinc finger protein 566) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=-2.14 with no splicing effect.
• 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	UniProt
ZNF566	NM_001145344.1	c.376C>A	p.Arg126=	synonymous_variant	5/5	ENST00000452939.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF566	ENST00000452939.7	c.376C>A	p.Arg126=	synonymous_variant	5/5	2	NM_001145344.1	P4

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86542 AN: 151814 Hom.: 25046 Cov.: 32

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.549

GnomAD3 exomes AF: 0.526 AC: 132234 AN: 251342 Hom.: 36610 AF XY: 0.536 AC XY: 72867 AN XY: 135852

Gnomad AFR exome AF: 0.617

Gnomad AMR exome AF: 0.322

Gnomad ASJ exome AF: 0.571

Gnomad EAS exome AF: 0.277

Gnomad SAS exome AF: 0.565

Gnomad FIN exome AF: 0.619

Gnomad NFE exome AF: 0.582

Gnomad OTH exome AF: 0.545

GnomAD4 exome AF: 0.568 AC: 829549 AN: 1461544 Hom.: 238719 Cov.: 60 AF XY: 0.568 AC XY: 413150 AN XY: 727082

Gnomad4 AFR exome AF: 0.614

Gnomad4 AMR exome AF: 0.335

Gnomad4 ASJ exome AF: 0.578

Gnomad4 EAS exome AF: 0.295

Gnomad4 SAS exome AF: 0.564

Gnomad4 FIN exome AF: 0.611

Gnomad4 NFE exome AF: 0.583

Gnomad4 OTH exome AF: 0.563

GnomAD4 genome AF: 0.570 AC: 86632 AN: 151932 Hom.: 25078 Cov.: 32 AF XY: 0.567 AC XY: 42119 AN XY: 74238

Gnomad4 AFR AF: 0.615

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.576

Gnomad4 FIN AF: 0.618

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.547

Alfa AF: 0.568 Hom.: 28832

Bravo AF: 0.555

Asia WGS AF: 0.471 AC: 1639 AN: 3478

EpiCase AF: 0.575

EpiControl AF: 0.589

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.82
Dann	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2967532; hg19: chr19-36940760; COSMIC: COSV67573242; COSMIC: COSV67573242;