Variant 15-84783201-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_014630.3(ZNF592):c.526G>A(p.Gly176Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000052 in 1,614,064 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 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

ZNF592
NM_014630.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.60

Variant links:

Genes affected

ZNF592 (HGNC:28986): (zinc finger protein 592) This gene is thought to play a role in a complex developmental pathway and the regulation of genes involved in cerebellar development. Mutations in this gene have been associated with autosomal recessive spinocerebellar ataxia. [provided by RefSeq, Jan 2011]

ZNF592 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=0.046252757).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF592	NM_014630.3 linkuse as main transcript	c.526G>A	p.Gly176Arg	missense_variant	4/11	ENST00000560079.7	NP_055445.2
ZNF592	XM_005254996.4 linkuse as main transcript	c.526G>A	p.Gly176Arg	missense_variant	3/10		XP_005255053.1
ZNF592	XM_011522246.3 linkuse as main transcript	c.526G>A	p.Gly176Arg	missense_variant	4/11		XP_011520548.1
ZNF592	XM_011522247.3 linkuse as main transcript	c.526G>A	p.Gly176Arg	missense_variant	3/10		XP_011520549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF592	ENST00000560079.7 linkuse as main transcript	c.526G>A	p.Gly176Arg	missense_variant	4/11	1	NM_014630.3	ENSP00000452877	P1
ZNF592	ENST00000559607.1 linkuse as main transcript	c.526G>A	p.Gly176Arg	missense_variant, NMD_transcript_variant	2/9	1		ENSP00000453491
ZNF592	ENST00000299927.4 linkuse as main transcript	c.526G>A	p.Gly176Arg	missense_variant	1/8	2		ENSP00000299927	P1

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000678

AC:

AN:

250730

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135702

show subpopulations

Gnomad AFR exome

AF:

0.000748

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000301

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000263

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.000893

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000122

Hom.:

Bravo

AF:

0.000283

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000988

AC:

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

Aug 04, 2021

The c.526G>A (p.G176R) alteration is located in exon 4 (coding exon 1) of the ZNF592 gene. This alteration results from a G to A substitution at nucleotide position 526, causing the glycine (G) at amino acid position 176 to be replaced by an arginine (R). 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

0.15

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.012

T;T

Eigen

Benign

0.0077

Eigen_PC

Benign

0.050

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.83

.;T

M_CAP

Benign

0.034

MetaRNN

Benign

0.046

T;T

MetaSVM

Benign

-0.56

MutationAssessor

Benign

0.34

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

0.30

N;N

REVEL

Benign

0.14

Sift

Benign

0.47

T;T

Sift4G

Benign

0.37

T;T

Polyphen

0.98

D;D

Vest4

0.39

MutPred

0.36

Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);

MVP

0.068

MPC

0.53

ClinPred

0.049

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.059

gMVP

0.070

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