20-18315175-C-G

Variant summary

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

The NM_001352452.2(ZNF133):​c.324C>G​(p.Phe108Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ZNF133
NM_001352452.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.84
Variant links:
Genes affected
ZNF133 (HGNC:12917): (zinc finger protein 133) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Predicted to be located 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=0.07105729).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF133NM_001352452.2 linkuse as main transcriptc.324C>G p.Phe108Leu missense_variant 7/7 ENST00000425686.3 NP_001339381.2
ZNF133-AS1XR_937299.4 linkuse as main transcriptn.574-1212G>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF133ENST00000425686.3 linkuse as main transcriptc.324C>G p.Phe108Leu missense_variant 7/73 NM_001352452.2 ENSP00000406638 A2P52736-1
ENST00000666293.1 linkuse as main transcriptn.425+8469G>C intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 30, 2024The c.321C>G (p.F107L) alteration is located in exon 7 (coding exon 3) of the ZNF133 gene. This alteration results from a C to G substitution at nucleotide position 321, causing the phenylalanine (F) at amino acid position 107 to be replaced by a leucine (L). 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
Pathogenic
0.61
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
8.1
DANN
Benign
0.87
DEOGEN2
Benign
0.031
.;.;T;.;.;T;.;.;.;.;T;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.69
T;T;.;T;T;T;.;T;T;T;.;T
M_CAP
Benign
0.0086
T
MetaRNN
Benign
0.071
T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
1.2
.;.;L;.;.;L;.;.;.;.;L;.
MutationTaster
Benign
1.0
N;N;N;N;N;N;N
PrimateAI
Benign
0.48
T
PROVEAN
Benign
-2.2
.;.;.;.;N;D;D;.;N;.;D;N
REVEL
Benign
0.076
Sift
Benign
0.083
.;.;.;.;T;T;T;.;T;.;T;T
Sift4G
Benign
0.11
T;T;T;T;T;T;T;T;T;T;T;T
Polyphen
0.010, 0.0030
.;B;B;.;.;B;B;.;.;.;B;.
Vest4
0.13
MutPred
0.26
.;.;Gain of disorder (P = 0.181);.;.;Gain of disorder (P = 0.181);.;.;Gain of disorder (P = 0.181);.;Gain of disorder (P = 0.181);Gain of disorder (P = 0.181);
MVP
0.28
MPC
0.44
ClinPred
0.071
T
GERP RS
-1.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.10
gMVP
0.049

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-18295819; API