19-52613159-C-T

Variant summary

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

The NM_018300.4(ZNF83):​c.1406G>A​(p.Arg469His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000856 in 1,612,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R469P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000091 ( 0 hom. )

Consequence

ZNF83
NM_018300.4 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.88
Variant links:
Genes affected
ZNF83 (HGNC:13158): (zinc finger protein 83) 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 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=0.055159926).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF83NM_001105549.2 linkc.1406G>A p.Arg469His missense_variant Exon 6 of 6 NP_001099019.1 P51522-1A0A024R4L3
ZNF83NM_001105550.2 linkc.1406G>A p.Arg469His missense_variant Exon 5 of 5 NP_001099020.1 P51522-1A0A024R4L3
ZNF83NM_001105551.2 linkc.1406G>A p.Arg469His missense_variant Exon 5 of 5 NP_001099021.1 P51522-1A0A024R4L3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF83ENST00000301096.8 linkc.1406G>A p.Arg469His missense_variant Exon 3 of 3 3 ENSP00000301096.3 P51522-1

Frequencies

GnomAD3 genomes
AF:
0.0000332
AC:
5
AN:
150692
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000244
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:
0.0000592
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000398
AC:
10
AN:
251320
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135824
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 SAS exome
AF:
0.0000654
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000704
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000910
AC:
133
AN:
1461432
Hom.:
0
Cov.:
31
AF XY:
0.0000949
AC XY:
69
AN XY:
726992
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000105
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000107
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000332
AC:
5
AN:
150692
Hom.:
0
Cov.:
33
AF XY:
0.0000408
AC XY:
3
AN XY:
73508
show subpopulations
Gnomad4 AFR
AF:
0.0000244
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000592
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000330
AC:
4
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
0.019
DANN
Benign
0.43
DEOGEN2
Benign
0.0019
T;T;T;T;T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.012
N
LIST_S2
Benign
0.051
.;T;.;.;.
M_CAP
Benign
0.0026
T
MetaRNN
Benign
0.055
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.27
N;N;N;N;N
PROVEAN
Benign
0.39
N;N;.;N;N
REVEL
Benign
0.015
Sift
Benign
0.64
T;T;.;T;T
Sift4G
Benign
0.58
T;T;T;T;T
Polyphen
0.91
P;P;P;P;P
Vest4
0.025
MVP
0.048
MPC
0.075
ClinPred
0.0057
T
GERP RS
-2.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.0087
gMVP
0.020

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: rs766361238; hg19: chr19-53116412; API