Variant 9-92847835-G-C 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_031486.4(ZNF484):c.952C>G(p.Arg318Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZNF484
NM_031486.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25

Variant links:

Genes affected

ZNF484 (HGNC:23385): (zinc finger protein 484) Predicted to enable DNA-binding transcription activator 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]

ZNF484 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=0.11777389).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF484	NM_031486.4 linkuse as main transcript	c.952C>G	p.Arg318Gly	missense_variant	5/5	ENST00000375495.8	NP_113674.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF484	ENST00000375495.8 linkuse as main transcript	c.952C>G	p.Arg318Gly	missense_variant	5/5	1	NM_031486.4	ENSP00000364645	P2	Q5JVG2-1
ZNF484	ENST00000395505.6 linkuse as main transcript	c.958C>G	p.Arg320Gly	missense_variant	4/4	2		ENSP00000378881	A2	Q5JVG2-3
ZNF484	ENST00000332591.6 linkuse as main transcript	c.844C>G	p.Arg282Gly	missense_variant	4/4	2		ENSP00000364646		Q5JVG2-2
ZNF484	ENST00000395506.7 linkuse as main transcript	c.844C>G	p.Arg282Gly	missense_variant	6/6	3		ENSP00000378882		Q5JVG2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461824

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727204

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 02, 2023

The c.952C>G (p.R318G) alteration is located in exon 5 (coding exon 4) of the ZNF484 gene. This alteration results from a C to G substitution at nucleotide position 952, causing the arginine (R) at amino acid position 318 to be replaced by a glycine (G). 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

0.094

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.0066

.;.;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0019

LIST_S2

Benign

0.0057

T;T;T;.

M_CAP

Benign

0.0018

MetaRNN

Benign

0.12

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

.;.;L;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.0

.;.;N;N

REVEL

Benign

0.024

Sift

Uncertain

0.0040

.;.;D;D

Sift4G

Uncertain

0.013

D;D;D;D

Polyphen

0.013

.;.;B;.

Vest4

0.13

MutPred

0.70

.;.;Gain of ubiquitination at K320 (P = 0.0231);.;

MVP

0.19

MPC

0.20

ClinPred

0.12

GERP RS

1.5

Varity_R

0.089

gMVP

0.034

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