Genetic Variant ZNF283:p.Glu132Lys (chr19-43846995-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_181845.2(ZNF283):c.394G>A(p.Glu132Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,561,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

ZNF283
NM_181845.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.598

Variant links:

Genes affected

ZNF283 (HGNC:13077): (zinc finger protein 283) 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 active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF283 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=0.098421544).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF283	NM_181845.2 link	c.394G>A	p.Glu132Lys	missense_variant	Exon 7 of 7	ENST00000618787.5	NP_862828.1	Q8N7M2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF283	ENST00000618787.5 link	c.394G>A	p.Glu132Lys	missense_variant	Exon 7 of 7	2	NM_181845.2	ENSP00000484852.1	Q8N7M2
ZNF283	ENST00000324461.9 link	c.394G>A	p.Glu132Lys	missense_variant	Exon 4 of 4	1		ENSP00000327314.7	Q8N7M2
ZNF283	ENST00000650832.1 link	c.286G>A	p.Glu96Lys	missense_variant	Exon 7 of 7			ENSP00000498705.1	A0A494C0U8
ZNF283	ENST00000588797.6 link	c.159G>A	p.Leu53Leu	synonymous_variant	Exon 6 of 6	2		ENSP00000468708.2	K7ESH0

Frequencies

GnomAD3 genomes

AF:

0.00000720

AC:

AN:

138818

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000157

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000204

AC:

AN:

196104

Hom.:

AF XY:

0.0000189

AC XY:

AN XY:

106094

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000459

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000211

AC:

AN:

1422540

Hom.:

Cov.:

AF XY:

0.0000142

AC XY:

AN XY:

706244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000266

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.00000720

AC:

AN:

138818

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

67330

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000157

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000902

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 04, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.394G>A (p.E132K) alteration is located in exon 7 (coding exon 4) of the ZNF283 gene. This alteration results from a G to A substitution at nucleotide position 394, causing the glutamic acid (E) at amino acid position 132 to be replaced by a lysine (K). 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

0.084

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

T;T

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.15

.;T

M_CAP

Benign

0.0076

MetaRNN

Benign

0.098

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.51

N;N

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-2.7

.;D

REVEL

Benign

0.084

Sift

Benign

0.17

.;T

Sift4G

Benign

0.23

T;T

Polyphen

0.38

B;B

Vest4

0.32

MutPred

0.34

Gain of ubiquitination at E132 (P = 0.0114);Gain of ubiquitination at E132 (P = 0.0114);

MVP

0.52

MPC

0.35

ClinPred

0.11

GERP RS

3.5

Varity_R

0.20

gMVP

0.083

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