chr9-92846412-A-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.2375T>Cā€‹(p.Ile792Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,008 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. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

ZNF484
NM_031486.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.556
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=0.091326386).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF484NM_031486.4 linkc.2375T>C p.Ile792Thr 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.2375T>C p.Ile792Thr missense_variant 5/51 NM_031486.4 ENSP00000364645.3 Q5JVG2-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152168
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461840
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727210
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
AF:
0.0000131
AC:
2
AN:
152168
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
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:
0.0000282
Hom.:
0
Bravo
AF:
0.0000113

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 GeneticsJul 26, 2024The c.2375T>C (p.I792T) alteration is located in exon 5 (coding exon 4) of the ZNF484 gene. This alteration results from a T to C substitution at nucleotide position 2375, causing the isoleucine (I) at amino acid position 792 to be replaced by a threonine (T). 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
Uncertain
0.35
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
16
DANN
Benign
0.83
DEOGEN2
Benign
0.0054
.;.;T;.
Eigen
Benign
-0.57
Eigen_PC
Benign
-0.54
FATHMM_MKL
Benign
0.0014
N
LIST_S2
Benign
0.19
T;T;T;.
M_CAP
Benign
0.0017
T
MetaRNN
Benign
0.091
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.64
.;.;N;.
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-1.4
.;.;N;N
REVEL
Benign
0.10
Sift
Benign
0.21
.;.;T;T
Sift4G
Benign
1.0
T;T;T;T
Polyphen
0.77
.;.;P;.
Vest4
0.20
MutPred
0.37
.;.;Loss of stability (P = 0.0042);.;
MVP
0.46
MPC
0.54
ClinPred
0.20
T
GERP RS
2.5
Varity_R
0.097
gMVP
0.026

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: rs1479185546; hg19: chr9-95608694; API