Variant 20-18315399-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001352452.2(ZNF133):c.548G>A(p.Gly183Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,614,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

ZNF133
NM_001352452.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.93

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.013626009).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF133	NM_001352452.2 linkuse as main transcript	c.548G>A	p.Gly183Glu	missense_variant	7/7	ENST00000425686.3	NP_001339381.2
ZNF133-AS1	XR_937299.4 linkuse as main transcript	n.574-1436C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF133	ENST00000425686.3 linkuse as main transcript	c.548G>A	p.Gly183Glu	missense_variant	7/7	3	NM_001352452.2	ENSP00000406638	A2	P52736-1
	ENST00000666293.1 linkuse as main transcript	n.425+8245C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152192

Hom.:

Cov.:

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:

0.000580

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000439

AC:

AN:

250802

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1461814

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000581

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000412

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

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

Mar 22, 2023

The c.545G>A (p.G182E) 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 545, causing the glycine (G) at amino acid position 182 to be replaced by a glutamic acid (E). 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

0.068

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.68

CADD

Benign

9.0

DANN

Benign

0.66

DEOGEN2

Benign

0.0082

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

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.094

LIST_S2

Benign

0.18

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

M_CAP

Benign

0.010

MetaRNN

Benign

0.014

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

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.1

.;.;L;.;.;L;.;.;.;L

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

1.1

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

REVEL

Benign

0.025

Sift

Benign

0.67

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

Sift4G

Benign

1.0

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

Polyphen

0.0

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

Vest4

0.085

MutPred

0.38

.;.;Gain of solvent accessibility (P = 0.0281);.;.;Gain of solvent accessibility (P = 0.0281);.;.;.;Gain of solvent accessibility (P = 0.0281);

MVP

0.22

MPC

0.50

ClinPred

0.025

GERP RS

1.9

Varity_R

0.025

gMVP

0.063

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over