19-52613513-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_018300.4(ZNF83):c.1052G>A(p.Gly351Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,614,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., 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: 1.82

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29854733).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
ZNF83	NM_001105549.2 link	c.1052G>A	p.Gly351Asp	missense_variant	Exon 6 of 6	NP_001099019.1	P51522-1A0A024R4L3
ZNF83	NM_001105550.2 link	c.1052G>A	p.Gly351Asp	missense_variant	Exon 5 of 5	NP_001099020.1	P51522-1A0A024R4L3
ZNF83	NM_001105551.2 link	c.1052G>A	p.Gly351Asp	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.1052G>A	p.Gly351Asp	missense_variant	Exon 3 of 3	3		ENSP00000301096.3		P51522-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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

GnomAD2 exomes

AF:

0.0000119

AC:

AN:

251382

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000867

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:

0.00000342

AC:

AN:

1461842

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.0000671

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1112000

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41422

American (AMR)

AF:

0.0000655

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2090

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 26, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1052G>A (p.G351D) alteration is located in exon 6 (coding exon 1) of the ZNF83 gene. This alteration results from a G to A substitution at nucleotide position 1052, causing the glycine (G) at amino acid position 351 to be replaced by an aspartic acid (D). 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.059

T;T;T;T;T

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.39

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.12

.;T;.;.;.

M_CAP

Benign

0.0060

MetaRNN

Benign

0.30

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;L;L;L;L

PhyloP100

1.8

PROVEAN

Pathogenic

-5.1

D;D;.;D;D

REVEL

Benign

0.095

Sift

Benign

0.083

T;T;.;T;T

Sift4G

Uncertain

0.043

D;D;D;D;D

Polyphen

1.0

D;D;D;D;D

Vest4

0.12

MutPred

0.53

Gain of ubiquitination at K352 (P = 0.05);Gain of ubiquitination at K352 (P = 0.05);Gain of ubiquitination at K352 (P = 0.05);Gain of ubiquitination at K352 (P = 0.05);Gain of ubiquitination at K352 (P = 0.05);

MVP

0.53

MPC

0.44

ClinPred

0.97

GERP RS

0.97

Varity_R

0.14

gMVP

0.027

Mutation Taster

=87/13

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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19-52613513-C-T

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