Variant chr19-52613711-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001277948.2(ZNF83):c.854G>C(p.Gly285Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000154 in 1,362,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0000063 ( 0 hom. )

Consequence

ZNF83
NM_001277948.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.36

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16167548).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF83	NM_018300.4 linkuse as main transcript	c.854G>C	p.Gly285Ala	missense_variant	3/3	ENST00000301096.8
ZNF83	NM_001277948.2 linkuse as main transcript	c.854G>C	p.Gly285Ala	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF83	ENST00000301096.8 linkuse as main transcript	c.854G>C	p.Gly285Ala	missense_variant	3/3	3	NM_018300.4	P1	P51522-1
	ENST00000702778.1 linkuse as main transcript	n.82-7388C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000128

AC:

AN:

101730

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000428

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000294

AC:

AN:

237718

Hom.:

AF XY:

0.0000154

AC XY:

AN XY:

129612

show subpopulations

Gnomad AFR exome

AF:

0.000311

Gnomad AMR exome

AF:

0.0000738

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000635

AC:

AN:

1260728

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

626160

show subpopulations

Gnomad4 AFR exome

AF:

0.000136

Gnomad4 AMR exome

AF:

0.0000847

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.99e-7

Gnomad4 OTH exome

AF:

0.0000200

GnomAD4 genome

AF:

0.000128

AC:

AN:

101796

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

49316

show subpopulations

Gnomad4 AFR

AF:

0.000427

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000126

Hom.:

Bravo

AF:

0.0000604

ESP6500AA

AF:

0.000913

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000404

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 01, 2022

The c.854G>C (p.G285A) alteration is located in exon 6 (coding exon 1) of the ZNF83 gene. This alteration results from a G to C substitution at nucleotide position 854, causing the glycine (G) at amino acid position 285 to be replaced by an alanine (A). 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

Pathogenic

0.61

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.075

T;T;T;T;T

Eigen

Benign

0.046

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.70

M_CAP

Benign

0.0071

MetaRNN

Benign

0.16

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.9

L;L;L;L;L

MutationTaster

Benign

1.0

D;D;N;N;N;N;N

PROVEAN

Pathogenic

-4.7

D;D;.;D;D

REVEL

Benign

0.091

Sift

Benign

0.047

D;D;.;D;D

Sift4G

Uncertain

0.022

D;D;D;D;D

Polyphen

1.0

D;D;D;D;D

Vest4

0.21

MVP

0.47

MPC

0.066

ClinPred

0.22

GERP RS

1.6

Varity_R

0.22

gMVP

0.039

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over