Genetic Variant ZNF263:p.Val534Ile (chr16-3290106-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005741.5(ZNF263):c.1600G>A(p.Val534Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,613,590 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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 0.0045 ( 7 hom., cov: 32)

Exomes 𝑓: 0.00088 ( 3 hom. )

Consequence

ZNF263
NM_005741.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.193

Publications

8 publications found

Variant links:

Genes affected

ZNF263 (HGNC:13056): (zinc finger protein 263) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and transcription cis-regulatory region binding activity. Involved in negative regulation of transcription by RNA polymerase II and positive regulation of transcription by RNA polymerase II. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF263 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038508475).

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF263	NM_005741.5 link	c.1600G>A	p.Val534Ile	missense_variant	Exon 6 of 6	ENST00000219069.6	NP_005732.2
ZNF263	NM_001411015.1 link	c.1600G>A	p.Val534Ile	missense_variant	Exon 6 of 8		NP_001397944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF263	ENST00000219069.6 link	c.1600G>A	p.Val534Ile	missense_variant	Exon 6 of 6	1	NM_005741.5	ENSP00000219069.5

Frequencies

GnomAD3 genomes

AF:

0.00449

AC:

681

AN:

151602

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0143

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00641

Gnomad NFE

AF:

0.000516

Gnomad OTH

AF:

0.00528

GnomAD2 exomes

AF:

0.00150

AC:

377

AN:

251360

AF XY:

0.00121

show subpopulations

Gnomad AFR exome

AF:

0.0138

Gnomad AMR exome

AF:

0.00194

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000554

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000876

AC:

1280

AN:

1461870

Hom.:

Cov.:

AF XY:

0.000784

AC XY:

570

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.0133

AC:

446

AN:

33480

American (AMR)

AF:

0.00186

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00111

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00156

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000556

AC:

618

AN:

1112004

Other (OTH)

AF:

0.00146

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

168

252

336

420

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<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:

0.00450

AC:

682

AN:

151720

Hom.:

Cov.:

AF XY:

0.00418

AC XY:

310

AN XY:

74132

show subpopulations

African (AFR)

AF:

0.0143

AC:

590

AN:

41380

American (AMR)

AF:

0.00275

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.000577

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5092

South Asian (SAS)

AF:

0.00

AC:

AN:

4768

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.00690

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000516

AC:

AN:

67878

Other (OTH)

AF:

0.00523

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

126

157

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00206

Hom.:

Bravo

AF:

0.00520

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0184

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00170

AC:

207

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.0051

T;T

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.00021

LIST_S2

Benign

0.54

T;T

MetaRNN

Benign

0.0039

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.28

.;N

PhyloP100

-0.19

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.020

N;N

REVEL

Benign

0.17

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.018

.;B

Vest4

0.027

MVP

0.048

MPC

0.57

ClinPred

0.017

GERP RS

4.8

PromoterAI

-0.0032

Neutral

(source)

Varity_R

0.041

gMVP

0.079

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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