chr9-92846319-T-G

Variant summary

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

The NM_031486.4(ZNF484):ā€‹c.2468A>Cā€‹(p.Gln823Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,614,056 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000033 ( 0 hom., cov: 32)
Exomes š‘“: 0.000024 ( 0 hom. )

Consequence

ZNF484
NM_031486.4 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.697
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]

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=0.17094111).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF484NM_031486.4 linkc.2468A>C p.Gln823Pro missense_variant 5/5 ENST00000375495.8 NP_113674.1 Q5JVG2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF484ENST00000375495.8 linkc.2468A>C p.Gln823Pro missense_variant 5/51 NM_031486.4 ENSP00000364645.3 Q5JVG2-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152198
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000294
Gnomad OTH
AF:
0.000959
GnomAD3 exomes
AF:
0.0000278
AC:
7
AN:
251438
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135892
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000578
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:
0.0000440
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000239
AC:
35
AN:
1461858
Hom.:
0
Cov.:
32
AF XY:
0.0000289
AC XY:
21
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000180
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152198
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.000959
Alfa
AF:
0.0000508
Hom.:
0
Bravo
AF:
0.0000378
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.000164
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsSep 11, 2024The c.2468A>C (p.Q823P) alteration is located in exon 5 (coding exon 4) of the ZNF484 gene. This alteration results from a A to C substitution at nucleotide position 2468, causing the glutamine (Q) at amino acid position 823 to be replaced by a proline (P). 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
0.083
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
18
DANN
Benign
0.83
DEOGEN2
Benign
0.18
.;.;T;.
Eigen
Benign
-0.51
Eigen_PC
Benign
-0.55
FATHMM_MKL
Benign
0.011
N
LIST_S2
Benign
0.36
T;T;T;.
M_CAP
Benign
0.0017
T
MetaRNN
Benign
0.17
T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Pathogenic
4.0
.;.;H;.
PrimateAI
Benign
0.22
T
PROVEAN
Uncertain
-3.5
.;.;D;D
REVEL
Benign
0.080
Sift
Uncertain
0.0020
.;.;D;D
Sift4G
Uncertain
0.0030
D;D;D;D
Polyphen
0.58
.;.;P;.
Vest4
0.26
MVP
0.58
MPC
0.18
ClinPred
0.30
T
GERP RS
2.3
Varity_R
0.55
gMVP
0.067

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.

Other links and lift over

dbSNP: rs745717554; hg19: chr9-95608601; API