19-20105283-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_007138.2(ZNF90):​c.193G>C​(p.Val65Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,510 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ZNF90
NM_007138.2 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.71

Publications

0 publications found
Variant links:
Genes affected
ZNF90 (HGNC:13165): (zinc finger protein 90) 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, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.036227763).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF90NM_007138.2 linkc.193G>C p.Val65Leu missense_variant Exon 3 of 4 ENST00000418063.3 NP_009069.1 Q03938

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF90ENST00000418063.3 linkc.193G>C p.Val65Leu missense_variant Exon 3 of 4 1 NM_007138.2 ENSP00000410466.2 Q03938
ZNF90ENST00000469078.5 linkn.193G>C non_coding_transcript_exon_variant Exon 3 of 6 5 ENSP00000420111.1 F8WDJ7
ZNF90ENST00000473524.5 linkn.193G>C non_coding_transcript_exon_variant Exon 3 of 5 3 ENSP00000418166.1 F8WBQ5
ZNF90ENST00000474284.1 linkn.205G>C non_coding_transcript_exon_variant Exon 2 of 4 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1455510
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
724164
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
33264
American (AMR)
AF:
0.00
AC:
0
AN:
44322
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25928
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39364
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86102
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52302
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5738
European-Non Finnish (NFE)
AF:
9.02e-7
AC:
1
AN:
1108488
Other (OTH)
AF:
0.00
AC:
0
AN:
60002
⚠️ 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: 0.275
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.83
CADD
Benign
0.17
DANN
Benign
0.24
DEOGEN2
Benign
0.00072
T
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.9
FATHMM_MKL
Benign
0.00081
N
LIST_S2
Benign
0.56
T
M_CAP
Benign
0.0015
T
MetaRNN
Benign
0.036
T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
0.74
N
PhyloP100
-1.7
PrimateAI
Benign
0.43
T
PROVEAN
Benign
0.32
N
REVEL
Benign
0.017
Sift
Benign
0.23
T
Sift4G
Benign
0.89
T
Polyphen
0.0
B
Vest4
0.12
MutPred
0.21
Loss of methylation at K66 (P = 0.0365);
MVP
0.040
MPC
0.0024
ClinPred
0.068
T
GERP RS
-1.1
Varity_R
0.078
gMVP
0.0032
Mutation Taster
=92/8
polymorphism

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

Other links and lift over

dbSNP: rs782489496; hg19: chr19-20216092; API