Variant 9-111527702-A-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_133464.5(ZNF483):c.307A>G(p.Ile103Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZNF483
NM_133464.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.204

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:

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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=0.0919306).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF483	NM_133464.5 linkuse as main transcript	c.307A>G	p.Ile103Val	missense_variant	2/6	ENST00000309235.6	NP_597721.2	Q8TF39-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF483	ENST00000309235.6 linkuse as main transcript	c.307A>G	p.Ile103Val	missense_variant	2/6	1	NM_133464.5	ENSP00000311679.5	Q8TF39-1
ZNF483	ENST00000355824.7 linkuse as main transcript	c.307A>G	p.Ile103Val	missense_variant	2/6	1		ENSP00000438048.1	Q6P088
ZNF483	ENST00000358151.8 linkuse as main transcript	c.307A>G	p.Ile103Val	missense_variant	2/6	2		ENSP00000350871.4	Q8TF39-2
ZNF483	ENST00000374374.3 linkuse as main transcript	c.307A>G	p.Ile103Val	missense_variant	2/2	2		ENSP00000363494.3	Q5VZN3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251306

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135858

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:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461834

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 25, 2024

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

0.20

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

8.9

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

.;T;.;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.61

T;T;T;T

M_CAP

Benign

0.0015

MetaRNN

Benign

0.092

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.;.;L

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.71

N;N;N;N

REVEL

Benign

0.047

Sift

Benign

0.14

T;T;T;T

Sift4G

Benign

0.24

T;T;T;T

Polyphen

0.0040, 0.50, 0.0010

.;B;P;B

Vest4

0.053

MutPred

0.52

Loss of catalytic residue at P105 (P = 0.0334);Loss of catalytic residue at P105 (P = 0.0334);Loss of catalytic residue at P105 (P = 0.0334);Loss of catalytic residue at P105 (P = 0.0334);

MVP

0.14

MPC

0.45

ClinPred

0.087

GERP RS

-0.75

Varity_R

0.031

gMVP

0.12

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