Variant chr20-23364393-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_022482.5(GZF1):c.10G>A(p.Gly4Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000083 in 1,565,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000078 ( 0 hom. )

Consequence

GZF1
NM_022482.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.09

Variant links:

Genes affected

GZF1 (HGNC:15808): (GDNF inducible zinc finger protein 1) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

GZF1 links:

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=0.17334667).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GZF1	NM_022482.5 linkuse as main transcript	c.10G>A	p.Gly4Ser	missense_variant	2/6	ENST00000338121.10	NP_071927.1	Q9H116-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GZF1	ENST00000338121.10 linkuse as main transcript	c.10G>A	p.Gly4Ser	missense_variant	2/6	1	NM_022482.5	ENSP00000338290.5	Q9H116-1
GZF1	ENST00000377051.2 linkuse as main transcript	c.10G>A	p.Gly4Ser	missense_variant	1/5	1		ENSP00000366250.2	Q9H116-1
GZF1	ENST00000424216.1 linkuse as main transcript	c.10G>A	p.Gly4Ser	missense_variant	3/3	5		ENSP00000410009.1	Q5JXG1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152184

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000778

AC:

AN:

1413376

Hom.:

Cov.:

AF XY:

0.00000860

AC XY:

AN XY:

697380

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:

0.0000101

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 19, 2022

This variant has not been reported in the literature in individuals affected with GZF1-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 4 of the GZF1 protein (p.Gly4Ser). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.019

T;.;T

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.68

.;T;T

M_CAP

Benign

0.0068

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

L;.;L

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.82

N;D;N

REVEL

Benign

0.036

Sift

Benign

0.15

T;T;T

Sift4G

Benign

0.12

T;T;T

Polyphen

0.95

P;.;P

Vest4

0.075

MutPred

0.16

Gain of phosphorylation at G4 (P = 0.023);Gain of phosphorylation at G4 (P = 0.023);Gain of phosphorylation at G4 (P = 0.023);

MVP

0.40

MPC

0.60

ClinPred

0.85

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.079

gMVP

0.21

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