12-133058870-G-A

Variant summary

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

The NM_001289971.2(ZNF84):​c.2155G>A​(p.Ala719Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,230 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ZNF84
NM_001289971.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.133
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 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=0.07920155).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF84NM_001289971.2 linkc.2155G>A p.Ala719Thr 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.2155G>A p.Ala719Thr missense_variant Exon 5 of 5 1 NM_001289971.2 ENSP00000445549.1 P51523

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152158
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.000957
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461072
Hom.:
0
Cov.:
36
AF XY:
0.00000275
AC XY:
2
AN XY:
726824
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.00
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152158
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000131
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:
0.000957
Bravo
AF:
0.0000718

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 31, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2155G>A (p.A719T) alteration is located in exon 5 (coding exon 4) of the ZNF84 gene. This alteration results from a G to A substitution at nucleotide position 2155, causing the alanine (A) at amino acid position 719 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
Benign
0.16
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
21
DANN
Benign
0.80
DEOGEN2
Benign
0.042
T;.;T;T
Eigen
Benign
-0.67
Eigen_PC
Benign
-0.60
FATHMM_MKL
Benign
0.059
N
LIST_S2
Benign
0.31
T;T;.;.
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.079
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.065
N;.;N;N
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-2.0
N;N;N;N
REVEL
Benign
0.050
Sift
Benign
0.14
T;T;T;T
Sift4G
Benign
0.50
T;T;T;T
Polyphen
0.26
B;.;B;B
Vest4
0.24
MutPred
0.45
Gain of catalytic residue at I714 (P = 0.0048);.;Gain of catalytic residue at I714 (P = 0.0048);Gain of catalytic residue at I714 (P = 0.0048);
MVP
0.11
ClinPred
0.086
T
GERP RS
1.8
Varity_R
0.048
gMVP
0.042

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: rs994233045; hg19: chr12-133635456; API