Variant 20-18315254-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001352452.2(ZNF133):c.403G>A(p.Glu135Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZNF133
NM_001352452.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.443

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]

ZNF133 links:

ZNF133 (HGNC:):

ZNF133 links:

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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=0.07532975).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF133	NM_001352452.2 linkuse as main transcript	c.403G>A	p.Glu135Lys	missense_variant	7/7	ENST00000425686.3	NP_001339381.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF133	ENST00000425686.3 linkuse as main transcript	c.403G>A	p.Glu135Lys	missense_variant	7/7	3	NM_001352452.2	ENSP00000406638.2		P52736-1Q5JXV9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Ambry Genetics

Jun 22, 2021

The c.400G>A (p.E134K) alteration is located in exon 7 (coding exon 3) of the ZNF133 gene. This alteration results from a G to A substitution at nucleotide position 400, causing the glutamic acid (E) at amino acid position 134 to be replaced by a lysine (K). 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

0.077

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

7.4

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0079

.;.;T;.;.;T;.;.;.;.;T;.

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.48

T;T;.;T;T;T;.;T;T;T;.;T

M_CAP

Benign

0.0058

MetaRNN

Benign

0.075

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.34

.;.;N;.;.;N;.;.;.;.;N;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.5

.;.;.;.;N;N;N;.;N;.;N;N

REVEL

Benign

0.10

Sift

Uncertain

0.027

.;.;.;.;D;T;T;.;T;.;T;T

Sift4G

Benign

0.36

T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.0070, 0.0040

.;B;B;.;.;B;B;.;.;.;B;.

Vest4

0.094

MutPred

0.33

.;.;Gain of ubiquitination at E135 (P = 0.0045);.;.;Gain of ubiquitination at E135 (P = 0.0045);.;.;Gain of ubiquitination at E135 (P = 0.0045);.;Gain of ubiquitination at E135 (P = 0.0045);Gain of ubiquitination at E135 (P = 0.0045);

MVP

0.43

MPC

0.45

ClinPred

0.085

GERP RS

3.0

Varity_R

0.061

gMVP

0.13

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over