19-20934051-A-G
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003429.5(ZNF85):c.31A>G(p.Ile11Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,612,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
ZNF85
NM_003429.5 missense
NM_003429.5 missense
Scores
19
Clinical Significance
Conservation
PhyloP100: 0.0990
Publications
0 publications found
Genes affected
ZNF85 (HGNC:13160): (zinc finger protein 85) Enables DNA-binding transcription repressor 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, DNA-templated. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12058687).
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.0000461 AC: 7AN: 151854Hom.: 0 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
7
AN:
151854
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00000398 AC: 1AN: 251282 AF XY: 0.00000736 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
251282
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460234Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 726410 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
4
AN:
1460234
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
726410
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
4
AN:
33428
American (AMR)
AF:
AC:
0
AN:
44648
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26062
East Asian (EAS)
AF:
AC:
0
AN:
39660
South Asian (SAS)
AF:
AC:
0
AN:
86224
European-Finnish (FIN)
AF:
AC:
0
AN:
53074
Middle Eastern (MID)
AF:
AC:
0
AN:
5760
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111064
Other (OTH)
AF:
AC:
0
AN:
60314
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.362
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000592 AC: 9AN: 151972Hom.: 0 Cov.: 31 AF XY: 0.0000673 AC XY: 5AN XY: 74282 show subpopulations
GnomAD4 genome
AF:
AC:
9
AN:
151972
Hom.:
Cov.:
31
AF XY:
AC XY:
5
AN XY:
74282
show subpopulations
African (AFR)
AF:
AC:
8
AN:
41466
American (AMR)
AF:
AC:
0
AN:
15216
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3466
East Asian (EAS)
AF:
AC:
0
AN:
5158
South Asian (SAS)
AF:
AC:
0
AN:
4820
European-Finnish (FIN)
AF:
AC:
0
AN:
10554
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
1
AN:
67984
Other (OTH)
AF:
AC:
0
AN:
2102
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.482
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
1
Asia WGS
AF:
AC:
3
AN:
3478
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Apr 17, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.31A>G (p.I11V) alteration is located in exon 2 (coding exon 2) of the ZNF85 gene. This alteration results from a A to G substitution at nucleotide position 31, causing the isoleucine (I) at amino acid position 11 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Benign
DEOGEN2
Benign
.;.;.;.;.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;N;.;.;N;N
PhyloP100
PrimateAI
Benign
T
PROVEAN
Benign
.;.;N;.;.;N;N
REVEL
Benign
Sift
Benign
.;.;T;.;.;T;T
Sift4G
Benign
T;T;T;T;T;T;T
Polyphen
0.72
.;.;.;.;.;P;.
Vest4
MutPred
Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);
MVP
MPC
0.0055
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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