chr7-64706893-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001282359.2(ZNF107):​c.796T>G​(p.Phe266Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,613,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZNF107
NM_001282359.2 missense

Scores

5
3
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.81

Publications

0 publications found
Variant links:
Genes affected
ZNF107 (HGNC:12887): (zinc finger protein 107) This gene encodes a protein containing multiple C2H2-type zinc finger regions. Proteins containing zinc fingers may act as transcriptional regulators, but may also have other cellular functions. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.751

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF107NM_001282359.2 linkc.796T>G p.Phe266Val missense_variant Exon 4 of 4 ENST00000620827.6 NP_001269288.1 A0A0B4J2G0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF107ENST00000620827.6 linkc.796T>G p.Phe266Val missense_variant Exon 4 of 4 4 NM_001282359.2 ENSP00000483720.1 A0A0B4J2G0

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152178
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460926
Hom.:
0
Cov.:
33
AF XY:
0.00000275
AC XY:
2
AN XY:
726748
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33412
American (AMR)
AF:
0.00
AC:
0
AN:
44624
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26022
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39676
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86138
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53306
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5758
European-Non Finnish (NFE)
AF:
0.00000180
AC:
2
AN:
1111654
Other (OTH)
AF:
0.00
AC:
0
AN:
60336
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152178
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74348
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41450
American (AMR)
AF:
0.00
AC:
0
AN:
15272
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5198
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10628
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
68008
Other (OTH)
AF:
0.00
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 02, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.589T>G (p.F197V) alteration is located in exon 7 (coding exon 2) of the ZNF107 gene. This alteration results from a T to G substitution at nucleotide position 589, causing the phenylalanine (F) at amino acid position 197 to be replaced by a valine (V). 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
Uncertain
0.44
BayesDel_addAF
Benign
-0.037
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
20
DANN
Benign
0.94
DEOGEN2
Benign
0.16
T;.;T;T;T
Eigen
Uncertain
0.20
Eigen_PC
Benign
-0.083
FATHMM_MKL
Benign
0.016
N
LIST_S2
Benign
0.10
T;T;.;T;.
M_CAP
Benign
0.0060
T
MetaRNN
Pathogenic
0.75
D;D;D;D;D
MetaSVM
Benign
-0.62
T
MutationAssessor
Pathogenic
3.7
.;.;H;H;H
PhyloP100
5.8
PrimateAI
Uncertain
0.50
T
PROVEAN
Pathogenic
-6.3
.;.;D;D;D
REVEL
Benign
0.18
Sift
Pathogenic
0.0
.;.;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D;D
Polyphen
1.0
.;.;D;D;D
Vest4
0.28
MutPred
0.82
.;.;Gain of ubiquitination at K198 (P = 0.0707);Gain of ubiquitination at K198 (P = 0.0707);Gain of ubiquitination at K198 (P = 0.0707);
MVP
0.18
MPC
0.038
ClinPred
0.91
D
GERP RS
1.4
Varity_R
0.52
gMVP
0.10
Mutation Taster
=98/2
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: rs1790669512; hg19: chr7-64167271; API