16-3283913-A-G

Variant summary

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

The NM_005741.5(ZNF263):​c.95A>G​(p.Asp32Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D32E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF263
NM_005741.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.85

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]

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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=0.07634807).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF263NM_005741.5 linkc.95A>G p.Asp32Gly missense_variant Exon 1 of 6 ENST00000219069.6 NP_005732.2 O14978
ZNF263NM_001411015.1 linkc.95A>G p.Asp32Gly 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.95A>G p.Asp32Gly missense_variant Exon 1 of 6 1 NM_005741.5 ENSP00000219069.5 O14978

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461120
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726888
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33478
American (AMR)
AF:
0.00
AC:
0
AN:
44710
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26126
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39688
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86250
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52814
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5750
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1111926
Other (OTH)
AF:
0.00
AC:
0
AN:
60378
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 07, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.95A>G (p.D32G) alteration is located in exon 1 (coding exon 1) of the ZNF263 gene. This alteration results from a A to G substitution at nucleotide position 95, causing the aspartic acid (D) at amino acid position 32 to be replaced by a glycine (G). 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
0.33
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
20
DANN
Benign
0.49
DEOGEN2
Benign
0.0087
T;.;T;.
Eigen
Benign
-0.91
Eigen_PC
Benign
-0.81
FATHMM_MKL
Benign
0.0014
N
LIST_S2
Benign
0.071
T;T;T;T
M_CAP
Benign
0.0066
T
MetaRNN
Benign
0.076
T;T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.020
N;.;.;.
PhyloP100
1.9
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-1.1
N;.;.;.
REVEL
Benign
0.071
Sift
Benign
0.20
T;.;.;.
Sift4G
Benign
0.66
T;T;T;T
Polyphen
0.010
B;.;.;.
Vest4
0.27
MutPred
0.18
Gain of catalytic residue at D32 (P = 0.023);Gain of catalytic residue at D32 (P = 0.023);Gain of catalytic residue at D32 (P = 0.023);Gain of catalytic residue at D32 (P = 0.023);
MVP
0.32
MPC
0.51
ClinPred
0.18
T
GERP RS
5.1
PromoterAI
-0.069
Neutral
Varity_R
0.15
gMVP
0.46
Mutation Taster
=94/6
polymorphism

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

Other links and lift over

hg19: chr16-3333913; API