9-111541688-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_133464.5(ZNF483):​c.753G>T​(p.Arg251Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,609,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ZNF483
NM_133464.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.363

Publications

0 publications found
Variant links:
Genes affected
ZNF483 (HGNC:23384): (zinc finger protein 483) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.028992802).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF483NM_133464.5 linkc.753G>T p.Arg251Ser missense_variant Exon 6 of 6 ENST00000309235.6 NP_597721.2 Q8TF39-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF483ENST00000309235.6 linkc.753G>T p.Arg251Ser missense_variant Exon 6 of 6 1 NM_133464.5 ENSP00000311679.5 Q8TF39-1
ZNF483ENST00000358151.8 linkc.721+7335G>T intron_variant Intron 5 of 5 2 ENSP00000350871.4 Q8TF39-2

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152096
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00000813
AC:
2
AN:
245876
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000598
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000412
AC:
6
AN:
1457020
Hom.:
0
Cov.:
31
AF XY:
0.00000552
AC XY:
4
AN XY:
724652
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33042
American (AMR)
AF:
0.0000922
AC:
4
AN:
43380
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25948
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39674
South Asian (SAS)
AF:
0.00
AC:
0
AN:
84988
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53346
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5746
European-Non Finnish (NFE)
AF:
9.00e-7
AC:
1
AN:
1110748
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60148
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.467
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152096
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74288
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41418
American (AMR)
AF:
0.00
AC:
0
AN:
15260
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5196
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4822
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10590
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000294
AC:
2
AN:
68018
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000756

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 03, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.753G>T (p.R251S) alteration is located in exon 6 (coding exon 5) of the ZNF483 gene. This alteration results from a G to T substitution at nucleotide position 753, causing the arginine (R) at amino acid position 251 to be replaced by a serine (S). 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
0.30
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
8.0
DANN
Benign
0.91
DEOGEN2
Benign
0.035
T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.0051
N
LIST_S2
Benign
0.51
T
M_CAP
Benign
0.0024
T
MetaRNN
Benign
0.029
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
1.2
L
PhyloP100
-0.36
PrimateAI
Benign
0.23
T
PROVEAN
Benign
0.41
N
REVEL
Benign
0.017
Sift
Benign
0.41
T
Sift4G
Benign
0.73
T
Polyphen
0.0020
B
Vest4
0.043
MutPred
0.52
Gain of phosphorylation at R251 (P = 0.0298);
MVP
0.17
MPC
0.69
ClinPred
0.027
T
GERP RS
-7.1
Varity_R
0.11
gMVP
0.22
Mutation Taster
=95/5
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

dbSNP: rs756197063; hg19: chr9-114303968; API