Genetic Variant ZNF83:p.Arg502Cys (chr19-52613061-G-A) – 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_018300.4(ZNF83):c.1504C>T(p.Arg502Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,458,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ZNF83
NM_018300.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -10.4

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]

ZNF83 links:

ENSG00000269825 (HGNC:):

ENSG00000269825 links:

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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=0.10365838).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
ZNF83	NM_001105549.2 link	c.1504C>T	p.Arg502Cys	missense_variant	Exon 6 of 6	NP_001099019.1	P51522-1A0A024R4L3
ZNF83	NM_001105550.2 link	c.1504C>T	p.Arg502Cys	missense_variant	Exon 5 of 5	NP_001099020.1	P51522-1A0A024R4L3
ZNF83	NM_001105551.2 link	c.1504C>T	p.Arg502Cys	missense_variant	Exon 5 of 5	NP_001099021.1	P51522-1A0A024R4L3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF83	ENST00000301096.8 link	c.1504C>T	p.Arg502Cys	missense_variant	Exon 3 of 3	3		ENSP00000301096.3		P51522-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000402

AC:

AN:

249050

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000293

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:

0.00000343

AC:

AN:

1458928

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725400

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33414

American (AMR)

AF:

0.0000226

AC:

AN:

44344

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25966

East Asian (EAS)

AF:

0.00

AC:

AN:

39642

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53342

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1110370

Other (OTH)

AF:

0.0000166

AC:

AN:

60286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 15, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1504C>T (p.R502C) alteration is located in exon 6 (coding exon 1) of the ZNF83 gene. This alteration results from a C to T substitution at nucleotide position 1504, causing the arginine (R) at amino acid position 502 to be replaced by a cysteine (C). 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

0.31

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.0050

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.0098

T;T;T;T;T

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0078

LIST_S2

Benign

0.56

.;T;.;.;.

M_CAP

Benign

0.011

MetaRNN

Benign

0.10

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

M;M;M;M;M

PhyloP100

-10

PROVEAN

Benign

-2.1

N;N;.;N;N

REVEL

Benign

0.080

Sift

Benign

0.10

T;T;.;T;T

Sift4G

Benign

0.13

T;T;T;T;T

Polyphen

0.0

B;B;B;B;B

Vest4

0.18

MutPred

0.43

Loss of MoRF binding (P = 0.0039);Loss of MoRF binding (P = 0.0039);Loss of MoRF binding (P = 0.0039);Loss of MoRF binding (P = 0.0039);Loss of MoRF binding (P = 0.0039);

MVP

0.088

MPC

0.082

ClinPred

0.045

GERP RS

-3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.040

gMVP

0.043

Mutation Taster

=100/0

polymorphism

(source)

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

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19-52613061-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over