dbSNP rs34236132: 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	O14978
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		O14978

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

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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