Genetic Variant ZNF566:p.Arg126Arg (chr19-36449858-G-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.14

Publications

19 publications found

Variant links:

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]

ZNF566 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF566	NM_001145344.1 link	c.376C>A	p.Arg126Arg	synonymous_variant	Exon 5 of 5	ENST00000452939.7	NP_001138816.1	Q969W8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF566	ENST00000452939.7 link	c.376C>A	p.Arg126Arg	synonymous_variant	Exon 5 of 5	2	NM_001145344.1	ENSP00000411526.2		Q969W8-1C9J6X1

Frequencies

GnomAD3 genomes

AF:

0.570

AC:

86542

AN:

151814

Hom.:

25046

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.568

AC XY:

413150

AN XY:

727082

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

20669

41338

62006

82675

103344

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17730

35460

53190

70920

88650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.570

AC:

86632

AN:

151932

Hom.:

25078

Cov.:

AF XY:

0.567

AC XY:

42119

AN XY:

74238

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1881

3763

5644

7526

9407

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

738

1476

2214

2952

3690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.82

(source)

DANN

Benign

0.36

PhyloP100

-2.1

PromoterAI

-0.019

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over