20-18315389-G-A

Position:

chr20-18315389-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001352452.2(ZNF133):c.538G>A(p.Gly180Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000142 in 1,614,184 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ZNF133
NM_001352452.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.560

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.052216798).

BP6

Variant 20-18315389-G-A is Benign according to our data. Variant chr20-18315389-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2471760.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF133	NM_001352452.2 linkuse as main transcript	c.538G>A	p.Gly180Ser	missense_variant	7/7	ENST00000425686.3	NP_001339381.2
ZNF133-AS1	XR_937299.4 linkuse as main transcript	n.574-1426C>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.538G>A	p.Gly180Ser	missense_variant	7/7	3	NM_001352452.2	ENSP00000406638	A2	P52736-1
	ENST00000666293.1 linkuse as main transcript	n.425+8255C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

250714

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135710

show subpopulations

Gnomad AFR exome

AF:

0.000187

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 07, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.68

CADD

Benign

7.5

DANN

Benign

0.73

DEOGEN2

Benign

0.0086

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

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.27

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

M_CAP

Benign

0.013

MetaRNN

Benign

0.052

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

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

MutationTaster

Benign

1.0

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

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.7

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

REVEL

Benign

0.14

Sift

Benign

0.24

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

Sift4G

Benign

0.18

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

Polyphen

0.94, 0.91

.;P;P;.;.;P;P;.;.;P

Vest4

0.048

MutPred

0.23

.;.;Gain of phosphorylation at G180 (P = 0.0075);.;.;Gain of phosphorylation at G180 (P = 0.0075);.;.;.;Gain of phosphorylation at G180 (P = 0.0075);

MVP

0.32

MPC

0.68

ClinPred

0.073

GERP RS

3.2

Varity_R

0.037

gMVP

0.086

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