19-36449858-G-T

Variant names:

• chr19-36449858-G-T
• rs2967532
• NM_001145344.1:c.376C>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001145344.1(ZNF566):​c.376C>A​(p.Arg126Arg) 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
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145344.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF566	NM_001145344.1	MANE Select	c.376C>A	p.Arg126Arg	synonymous	Exon 5 of 5	NP_001138816.1	Q969W8-1
	ZNF566	NM_001145343.1		c.379C>A	p.Arg127Arg	synonymous	Exon 5 of 5	NP_001138815.1	Q969W8-2
	ZNF566	NM_001437584.1		c.379C>A	p.Arg127Arg	synonymous	Exon 5 of 5	NP_001424513.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF566	ENST00000452939.7	TSL:2 MANE Select	c.376C>A	p.Arg126Arg	synonymous	Exon 5 of 5	ENSP00000411526.2	Q969W8-1
	ZNF566	ENST00000493391.6	TSL:1	c.64C>A	p.Arg22Arg	synonymous	Exon 3 of 3	ENSP00000465343.1	B4DRR6
	ZNF566	ENST00000392170.7	TSL:5	c.379C>A	p.Arg127Arg	synonymous	Exon 5 of 5	ENSP00000376010.2	Q969W8-2

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

GnomAD2 exomes AF: 0.526 AC: 132234 AN: 251342 AF XY: 0.536

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 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

African (AFR) AF: 0.614 AC: 20566 AN: 33476

American (AMR) AF: 0.335 AC: 14989 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 15114 AN: 26128

East Asian (EAS) AF: 0.295 AC: 11692 AN: 39686

South Asian (SAS) AF: 0.564 AC: 48669 AN: 86240

European-Finnish (FIN) AF: 0.611 AC: 32612 AN: 53406

Middle Eastern (MID) AF: 0.630 AC: 3631 AN: 5768

European-Non Finnish (NFE) AF: 0.583 AC: 648294 AN: 1111734

Other (OTH) AF: 0.563 AC: 33982 AN: 60382

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

African (AFR) AF: 0.615 AC: 25438 AN: 41388

American (AMR) AF: 0.451 AC: 6880 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1995 AN: 3468

East Asian (EAS) AF: 0.279 AC: 1435 AN: 5150

South Asian (SAS) AF: 0.576 AC: 2776 AN: 4822

European-Finnish (FIN) AF: 0.618 AC: 6527 AN: 10558

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.585 AC: 39770 AN: 67974

Other (OTH) AF: 0.547 AC: 1151 AN: 2104

Alfa AF: 0.567 Hom.: 40246

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.82
DANN	Benign	0.36
PhyloP100		-2.1
PromoterAI		-0.019	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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