12-133057003-C-G

Variant summary

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

The NM_001289971.2(ZNF84):​c.288C>G​(p.Asp96Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,450,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZNF84
NM_001289971.2 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.172
Variant links:
Genes affected
ZNF84 (HGNC:13159): (zinc finger protein 84) 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]

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=0.03476581).
BP6
Variant 12-133057003-C-G is Benign according to our data. Variant chr12-133057003-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2470748.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF84NM_001289971.2 linkc.288C>G p.Asp96Glu missense_variant Exon 5 of 5 ENST00000539354.6 NP_001276900.1 P51523

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF84ENST00000539354.6 linkc.288C>G p.Asp96Glu missense_variant Exon 5 of 5 1 NM_001289971.2 ENSP00000445549.1 P51523

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000138
AC:
2
AN:
1450834
Hom.:
0
Cov.:
33
AF XY:
0.00000139
AC XY:
1
AN XY:
721420
show subpopulations
Gnomad4 AFR exome
AF:
0.0000306
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:
9.02e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Feb 15, 2023
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
0.064
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
11
DANN
Benign
0.96
DEOGEN2
Benign
0.0088
T;.;T;T;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.017
N
LIST_S2
Benign
0.036
T;T;.;T;.
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.035
T;T;T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
1.5
L;.;L;.;L
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-1.1
N;N;N;N;N
REVEL
Benign
0.029
Sift
Benign
0.52
T;T;T;T;T
Sift4G
Benign
1.0
T;T;T;T;T
Polyphen
0.0
B;.;B;.;B
Vest4
0.012
MutPred
0.23
Gain of helix (P = 0.0854);.;Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);
MVP
0.13
ClinPred
0.052
T
GERP RS
-1.1
Varity_R
0.026
gMVP
0.015

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: rs1954170854; hg19: chr12-133633589; API