16-3283886-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005741.5(ZNF263):​c.68C>T​(p.Ala23Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000652 in 1,610,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

ZNF263
NM_005741.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00700
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.030735105).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF263NM_005741.5 linkc.68C>T p.Ala23Val missense_variant Exon 1 of 6 ENST00000219069.6 NP_005732.2 O14978
ZNF263NM_001411015.1 linkc.68C>T p.Ala23Val missense_variant Exon 1 of 8 NP_001397944.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF263ENST00000219069.6 linkc.68C>T p.Ala23Val missense_variant Exon 1 of 6 1 NM_005741.5 ENSP00000219069.5 O14978
ENSG00000290183ENST00000703449.1 linkc.-170-5507C>T intron_variant Intron 1 of 1 ENSP00000515300.1 B4DI05

Frequencies

GnomAD3 genomes
AF:
0.0000788
AC:
12
AN:
152236
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000525
AC:
13
AN:
247496
Hom.:
0
AF XY:
0.0000596
AC XY:
8
AN XY:
134198
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000585
Gnomad ASJ exome
AF:
0.000201
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000802
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000638
AC:
93
AN:
1457954
Hom.:
0
Cov.:
31
AF XY:
0.0000607
AC XY:
44
AN XY:
725366
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000675
Gnomad4 ASJ exome
AF:
0.000537
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000697
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000531
Gnomad4 OTH exome
AF:
0.000133
GnomAD4 genome
AF:
0.0000788
AC:
12
AN:
152236
Hom.:
0
Cov.:
32
AF XY:
0.000108
AC XY:
8
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00115
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000132
Hom.:
0
Bravo
AF:
0.0000831
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.000164
EpiControl
AF:
0.0000594

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 07, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.68C>T (p.A23V) 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 68, causing the alanine (A) at amino acid position 23 to be replaced by a valine (V). 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
0.16
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
19
DANN
Benign
0.88
DEOGEN2
Benign
0.019
T;.;T;.
Eigen
Benign
-0.78
Eigen_PC
Benign
-0.67
FATHMM_MKL
Benign
0.0017
N
LIST_S2
Benign
0.039
T;T;T;T
M_CAP
Benign
0.0030
T
MetaRNN
Benign
0.031
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.53
N;.;.;.
PrimateAI
Benign
0.48
T
PROVEAN
Benign
-0.81
N;.;.;.
REVEL
Benign
0.046
Sift
Benign
0.29
T;.;.;.
Sift4G
Benign
0.20
T;T;T;T
Polyphen
0.0010
B;.;.;.
Vest4
0.036
MVP
0.048
MPC
0.19
ClinPred
0.043
T
GERP RS
0.95
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.050
gMVP
0.25

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs368525401; hg19: chr16-3333886; API