Genetic Variant ZNF263:p.Pro5Leu (chr16-3283832-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005741.5(ZNF263):c.14C>T(p.Pro5Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000211 in 1,422,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZNF263
NM_005741.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0590

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.088867694).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF263	NM_005741.5 link	c.14C>T	p.Pro5Leu	missense_variant	Exon 1 of 6	ENST00000219069.6	NP_005732.2	O14978
ZNF263	NM_001411015.1 link	c.14C>T	p.Pro5Leu	missense_variant	Exon 1 of 8		NP_001397944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF263	ENST00000219069.6 link	c.14C>T	p.Pro5Leu	missense_variant	Exon 1 of 6	1	NM_005741.5	ENSP00000219069.5		O14978

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000449

AC:

AN:

222478

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000960

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000211

AC:

AN:

1422778

Hom.:

Cov.:

AF XY:

0.00000283

AC XY:

AN XY:

706142

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32250

American (AMR)

AF:

0.00

AC:

AN:

39742

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24282

East Asian (EAS)

AF:

0.00

AC:

AN:

39026

South Asian (SAS)

AF:

0.00

AC:

AN:

83198

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45440

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4878

European-Non Finnish (NFE)

AF:

0.00000274

AC:

AN:

1095362

Other (OTH)

AF:

0.00

AC:

AN:

58600

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 25, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.14C>T (p.P5L) alteration is located in exon 1 (coding exon 1) of the ZNF263 gene. This alteration results from a C to T substitution at nucleotide position 14, causing the proline (P) at amino acid position 5 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.036

T;.;T;.

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.0017

LIST_S2

Benign

0.65

T;T;T;T

M_CAP

Benign

0.0039

MetaRNN

Benign

0.089

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.3

L;.;.;.

PhyloP100

0.059

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.7

N;.;.;.

REVEL

Benign

0.029

Sift

Uncertain

0.0060

D;.;.;.

Sift4G

Uncertain

0.041

D;T;T;D

Polyphen

0.014

B;.;.;.

Vest4

0.27

MutPred

0.28

Loss of glycosylation at P5 (P = 0.0156);Loss of glycosylation at P5 (P = 0.0156);Loss of glycosylation at P5 (P = 0.0156);Loss of glycosylation at P5 (P = 0.0156);

MVP

0.14

MPC

0.23

ClinPred

0.23

GERP RS

3.1

PromoterAI

0.063

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.045

gMVP

0.47

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over