dbSNP rs778743816: ZNF83:p.Gly439Cys (chr19-52613250-C-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.1315G>T(p.Gly439Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,090 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. 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. G439R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ZNF83
NM_018300.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.745

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:

Genome browser will be placed here

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=0.10480344).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
ZNF83	NM_001105549.2 link	c.1315G>T	p.Gly439Cys	missense_variant	Exon 6 of 6	NP_001099019.1	P51522-1A0A024R4L3
ZNF83	NM_001105550.2 link	c.1315G>T	p.Gly439Cys	missense_variant	Exon 5 of 5	NP_001099020.1	P51522-1A0A024R4L3
ZNF83	NM_001105551.2 link	c.1315G>T	p.Gly439Cys	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.1315G>T	p.Gly439Cys	missense_variant	Exon 3 of 3	3		ENSP00000301096.3		P51522-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249486

AF XY:

0.00000741

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459090

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725812

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33412

American (AMR)

AF:

0.00

AC:

AN:

44186

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26060

East Asian (EAS)

AF:

0.00

AC:

AN:

39400

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85718

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53366

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110920

Other (OTH)

AF:

0.00

AC:

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0035

T;T;T;T;T

Eigen

Benign

-0.98

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.22

.;T;.;.;.

M_CAP

Benign

0.0069

MetaRNN

Benign

0.10

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.45

N;N;N;N;N

PhyloP100

-0.74

PROVEAN

Benign

-1.4

N;N;.;N;N

REVEL

Benign

0.051

Sift

Benign

0.073

T;T;.;T;T

Sift4G

Benign

0.094

T;T;T;T;T

Polyphen

0.98

D;D;D;D;D

Vest4

0.062

MutPred

0.34

Loss of disorder (P = 0.0696);Loss of disorder (P = 0.0696);Loss of disorder (P = 0.0696);Loss of disorder (P = 0.0696);Loss of disorder (P = 0.0696);

MVP

0.16

MPC

0.32

ClinPred

0.20

GERP RS

-0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.055

gMVP

0.013

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over