12-133057411-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001289971.2(ZNF84):​c.696C>A​(p.Asp232Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,614,174 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0012 ( 2 hom. )

Consequence

ZNF84
NM_001289971.2 missense

Scores

1
18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.02
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 Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.029776156).
BP6
Variant 12-133057411-C-A is Benign according to our data. Variant chr12-133057411-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2235653.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF84NM_001289971.2 linkc.696C>A p.Asp232Glu 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.696C>A p.Asp232Glu missense_variant Exon 5 of 5 1 NM_001289971.2 ENSP00000445549.1 P51523

Frequencies

GnomAD3 genomes
AF:
0.000624
AC:
95
AN:
152224
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000217
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000523
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:
0.00113
Gnomad OTH
AF:
0.000478
GnomAD4 exome
AF:
0.00115
AC:
1685
AN:
1461832
Hom.:
2
Cov.:
35
AF XY:
0.00112
AC XY:
816
AN XY:
727208
show subpopulations
Gnomad4 AFR exome
AF:
0.000179
Gnomad4 AMR exome
AF:
0.000268
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000937
Gnomad4 NFE exome
AF:
0.00143
Gnomad4 OTH exome
AF:
0.00118
GnomAD4 genome
AF:
0.000624
AC:
95
AN:
152342
Hom.:
0
Cov.:
33
AF XY:
0.000577
AC XY:
43
AN XY:
74508
show subpopulations
Gnomad4 AFR
AF:
0.000216
Gnomad4 AMR
AF:
0.000523
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00113
Gnomad4 OTH
AF:
0.000473
Bravo
AF:
0.000733

ClinVar

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

Submissions by phenotype

not specified Benign:1
Jul 14, 2021
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
0.083
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
0.55
DANN
Benign
0.51
DEOGEN2
Benign
0.0084
T;.;T;T;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.014
N
LIST_S2
Benign
0.022
T;T;.;T;.
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.030
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.61
N;.;N;.;N
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
1.5
N;N;N;N;N
REVEL
Benign
0.052
Sift
Benign
1.0
T;T;T;T;T
Sift4G
Benign
1.0
T;T;T;T;T
Polyphen
0.0
B;.;B;.;B
Vest4
0.031
MutPred
0.48
Gain of catalytic residue at A234 (P = 0.0014);.;Gain of catalytic residue at A234 (P = 0.0014);Gain of catalytic residue at A234 (P = 0.0014);Gain of catalytic residue at A234 (P = 0.0014);
MVP
0.13
ClinPred
0.023
T
GERP RS
-2.3
Varity_R
0.024
gMVP
0.014

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: rs201095617; hg19: chr12-133633997; API