Genetic Variant ZNF483:p.Asn163Ser (chr9-111530950-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_133464.5(ZNF483):c.488A>G(p.Asn163Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000203 in 1,527,164 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000021 ( 3 hom. )

Consequence

ZNF483
NM_133464.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.294

Publications

0 publications found

Variant links:

Genes affected

ZNF483 (HGNC:23384): (zinc finger protein 483) 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]

ZNF483 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03544435).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF483	NM_133464.5 link	c.488A>G	p.Asn163Ser	missense_variant	Exon 3 of 6	ENST00000309235.6	NP_597721.2	Q8TF39-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF483	ENST00000309235.6 link	c.488A>G	p.Asn163Ser	missense_variant	Exon 3 of 6	1	NM_133464.5	ENSP00000311679.5	Q8TF39-1
ZNF483	ENST00000355824.7 link	c.488A>G	p.Asn163Ser	missense_variant	Exon 3 of 6	1		ENSP00000438048.1	Q6P088
ZNF483	ENST00000358151.8 link	c.488A>G	p.Asn163Ser	missense_variant	Exon 3 of 6	2		ENSP00000350871.4	Q8TF39-2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151438

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:

0.000419

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000501

AC:

AN:

239498

AF XY:

0.0000617

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:

0.0000211

AC:

AN:

1375726

Hom.:

Cov.:

AF XY:

0.0000263

AC XY:

AN XY:

685272

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31738

American (AMR)

AF:

0.00

AC:

AN:

41818

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23626

East Asian (EAS)

AF:

0.00

AC:

AN:

37024

South Asian (SAS)

AF:

0.000245

AC:

AN:

77496

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48104

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5416

European-Non Finnish (NFE)

AF:

0.00000663

AC:

AN:

1055080

Other (OTH)

AF:

0.0000541

AC:

AN:

55424

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151438

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73900

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41278

American (AMR)

AF:

0.00

AC:

AN:

15172

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5148

South Asian (SAS)

AF:

0.000419

AC:

AN:

4778

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10474

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67820

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000312

Hom.:

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 28, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.488A>G (p.N163S) alteration is located in exon 3 (coding exon 2) of the ZNF483 gene. This alteration results from a A to G substitution at nucleotide position 488, causing the asparagine (N) at amino acid position 163 to be replaced by a serine (S). 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

0.080

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.72

(source)

DANN

Benign

0.18

DEOGEN2

Benign

0.0026

.;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0072

LIST_S2

Benign

0.28

T;T;T

M_CAP

Benign

0.0041

MetaRNN

Benign

0.035

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.045

N;.;N

PhyloP100

-0.29

PrimateAI

Benign

0.27

PROVEAN

Benign

0.090

N;N;N

REVEL

Benign

0.012

Sift

Benign

0.74

T;T;T

Sift4G

Benign

0.76

T;T;T

Polyphen

0.0050

.;B;B

Vest4

0.13

MutPred

0.18

Gain of phosphorylation at N163 (P = 0.0454);Gain of phosphorylation at N163 (P = 0.0454);Gain of phosphorylation at N163 (P = 0.0454);

MVP

0.19

MPC

0.56

ClinPred

0.014

GERP RS

-0.54

Varity_R

0.024

gMVP

0.040

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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9-111530950-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over