9-111530961-T-C

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_133464.5(ZNF483):c.499T>C(p.Cys167Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000128 in 1,481,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000073 ( 0 hom., cov: 27)

Exomes 𝑓: 0.0000060 ( 0 hom. )

Consequence

ZNF483
NM_133464.5 missense, splice_region

Scores

Splicing: ADA: 0.00001667

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.68

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.015699565).

BP6

Variant 9-111530961-T-C is Benign according to our data. Variant chr9-111530961-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3821268.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF483	NM_133464.5 link	c.499T>C	p.Cys167Arg	missense_variant, splice_region_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.499T>C	p.Cys167Arg	missense_variant, splice_region_variant	Exon 3 of 6	1	NM_133464.5	ENSP00000311679.5	Q8TF39-1
ZNF483	ENST00000355824.7 link	c.499T>C	p.Cys167Arg	missense_variant, splice_region_variant	Exon 3 of 6	1		ENSP00000438048.1	Q6P088
ZNF483	ENST00000358151.8 link	c.499T>C	p.Cys167Arg	missense_variant, splice_region_variant	Exon 3 of 6	2		ENSP00000350871.4	Q8TF39-2

Frequencies

GnomAD3 genomes

AF:

0.0000726

AC:

AN:

151570

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000194

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000198

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:

0.0000216

AC:

AN:

231124

Hom.:

AF XY:

0.0000319

AC XY:

AN XY:

125474

show subpopulations

Gnomad AFR exome

AF:

0.000274

Gnomad AMR exome

AF:

0.0000332

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:

0.00000601

AC:

AN:

1330278

Hom.:

Cov.:

AF XY:

0.00000905

AC XY:

AN XY:

663234

show subpopulations

Gnomad4 AFR exome

AF:

0.000131

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:

0.00

Gnomad4 OTH exome

AF:

0.0000754

GnomAD4 genome

AF:

0.0000725

AC:

AN:

151686

Hom.:

Cov.:

AF XY:

0.0000675

AC XY:

AN XY:

74104

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000197

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:

0.00000601

Hom.:

Bravo

AF:

0.0000756

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Feb 26, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.036

DANN

Benign

0.12

DEOGEN2

Benign

0.0029

.;T;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.00040

LIST_S2

Benign

0.050

T;T;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.016

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.67

N;.;N

PrimateAI

Benign

0.17

PROVEAN

Benign

0.46

N;N;N

REVEL

Benign

0.0020

Sift

Benign

0.70

T;T;T

Sift4G

Benign

0.91

T;T;T

Polyphen

0.0

.;B;B

Vest4

0.15

MVP

0.11

MPC

1.2

ClinPred

0.0091

GERP RS

-7.3

Varity_R

0.076

gMVP

0.076

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000017

dbscSNV1_RF

Benign

0.030

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