12-133058535-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001289971.2(ZNF84):​c.1820C>G​(p.Ala607Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000522 in 1,613,982 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00055 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00052 ( 3 hom. )

Consequence

ZNF84
NM_001289971.2 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.326
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 -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0516015).
BS2
High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF84NM_001289971.2 linkc.1820C>G p.Ala607Gly 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.1820C>G p.Ala607Gly missense_variant Exon 5 of 5 1 NM_001289971.2 ENSP00000445549.1 P51523

Frequencies

GnomAD3 genomes
AF:
0.000546
AC:
83
AN:
152138
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00151
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000735
Gnomad OTH
AF:
0.000959
GnomAD4 exome
AF:
0.000520
AC:
760
AN:
1461726
Hom.:
3
Cov.:
36
AF XY:
0.000535
AC XY:
389
AN XY:
727160
show subpopulations
Gnomad4 AFR exome
AF:
0.0000897
Gnomad4 AMR exome
AF:
0.000515
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000800
Gnomad4 FIN exome
AF:
0.0000375
Gnomad4 NFE exome
AF:
0.000526
Gnomad4 OTH exome
AF:
0.000662
GnomAD4 genome
AF:
0.000545
AC:
83
AN:
152256
Hom.:
0
Cov.:
33
AF XY:
0.000524
AC XY:
39
AN XY:
74448
show subpopulations
Gnomad4 AFR
AF:
0.0000962
Gnomad4 AMR
AF:
0.00150
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000735
Gnomad4 OTH
AF:
0.000949
Alfa
AF:
0.000641
Hom.:
0
Bravo
AF:
0.000578

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 18, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1820C>G (p.A607G) alteration is located in exon 5 (coding exon 4) of the ZNF84 gene. This alteration results from a C to G substitution at nucleotide position 1820, causing the alanine (A) at amino acid position 607 to be replaced by a glycine (G). 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
0.17
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.056
T;.;T;T
Eigen
Benign
-0.73
Eigen_PC
Benign
-0.62
FATHMM_MKL
Benign
0.041
N
LIST_S2
Benign
0.62
T;T;.;.
M_CAP
Benign
0.0093
T
MetaRNN
Benign
0.052
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.80
N;.;N;N
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-2.3
N;N;N;N
REVEL
Benign
0.051
Sift
Benign
0.052
T;D;T;T
Sift4G
Benign
0.11
T;T;T;T
Polyphen
0.0010
B;.;B;B
Vest4
0.16
MutPred
0.46
Gain of catalytic residue at C604 (P = 0.0523);.;Gain of catalytic residue at C604 (P = 0.0523);Gain of catalytic residue at C604 (P = 0.0523);
MVP
0.12
ClinPred
0.25
T
GERP RS
2.8
Varity_R
0.17
gMVP
0.19

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: rs201713110; hg19: chr12-133635121; API