rs8182086

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014630.3(ZNF592):c.2777G>A(p.Ser926Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,613,784 control chromosomes in the GnomAD database, including 55,769 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6480 hom., cov: 32)

Exomes 𝑓: 0.25 ( 49289 hom. )

Consequence

ZNF592
NM_014630.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.961

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030214787).

BP6

Variant 15-84798628-G-A is Benign according to our data. Variant chr15-84798628-G-A is described in ClinVar as [Benign]. Clinvar id is 130840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-84798628-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF592	NM_014630.3 linkuse as main transcript	c.2777G>A	p.Ser926Asn	missense_variant	8/11	ENST00000560079.7	NP_055445.2
ZNF592	XM_005254996.4 linkuse as main transcript	c.2777G>A	p.Ser926Asn	missense_variant	7/10		XP_005255053.1
ZNF592	XM_011522246.3 linkuse as main transcript	c.2777G>A	p.Ser926Asn	missense_variant	8/11		XP_011520548.1
ZNF592	XM_011522247.3 linkuse as main transcript	c.2777G>A	p.Ser926Asn	missense_variant	7/10		XP_011520549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF592	ENST00000560079.7 linkuse as main transcript	c.2777G>A	p.Ser926Asn	missense_variant	8/11	1	NM_014630.3	ENSP00000452877	P1
ZNF592	ENST00000559607.1 linkuse as main transcript	c.*189G>A		3_prime_UTR_variant, NMD_transcript_variant	6/9	1		ENSP00000453491
ZNF592	ENST00000299927.4 linkuse as main transcript	c.2777G>A	p.Ser926Asn	missense_variant	5/8	2		ENSP00000299927	P1

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42707

AN:

151980

Hom.:

6471

Cov.:

show subpopulations

Gnomad AFR

AF:

0.340

Gnomad AMI

AF:

0.202

Gnomad AMR

AF:

0.338

Gnomad ASJ

AF:

0.224

Gnomad EAS

AF:

0.460

Gnomad SAS

AF:

0.411

Gnomad FIN

AF:

0.227

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.223

Gnomad OTH

AF:

0.270

GnomAD3 exomes

AF:

0.298

AC:

74756

AN:

251016

Hom.:

12490

AF XY:

0.294

AC XY:

39879

AN XY:

135740

show subpopulations

Gnomad AFR exome

AF:

0.347

Gnomad AMR exome

AF:

0.427

Gnomad ASJ exome

AF:

0.218

Gnomad EAS exome

AF:

0.478

Gnomad SAS exome

AF:

0.394

Gnomad FIN exome

AF:

0.229

Gnomad NFE exome

AF:

0.218

Gnomad OTH exome

AF:

0.264

GnomAD4 exome

AF:

0.251

AC:

367335

AN:

1461686

Hom.:

49289

Cov.:

AF XY:

0.254

AC XY:

184380

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.348

Gnomad4 AMR exome

AF:

0.414

Gnomad4 ASJ exome

AF:

0.218

Gnomad4 EAS exome

AF:

0.432

Gnomad4 SAS exome

AF:

0.395

Gnomad4 FIN exome

AF:

0.234

Gnomad4 NFE exome

AF:

0.226

Gnomad4 OTH exome

AF:

0.262

GnomAD4 genome

AF:

0.281

AC:

42747

AN:

152098

Hom.:

6480

Cov.:

AF XY:

0.287

AC XY:

21355

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.340

Gnomad4 AMR

AF:

0.338

Gnomad4 ASJ

AF:

0.224

Gnomad4 EAS

AF:

0.459

Gnomad4 SAS

AF:

0.411

Gnomad4 FIN

AF:

0.227

Gnomad4 NFE

AF:

0.223

Gnomad4 OTH

AF:

0.267

Alfa

AF:

0.233

Hom.:

9918

Bravo

AF:

0.290

TwinsUK

AF:

0.227

AC:

842

ALSPAC

AF:

0.245

AC:

945

ESP6500AA

AF:

0.328

AC:

1446

ESP6500EA

AF:

0.219

AC:

1887

ExAC

AF:

0.292

AC:

35470

Asia WGS

AF:

0.425

AC:

1476

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -

Galloway-Mowat syndrome 1

Benign:1

Benign, no assertion criteria provided

clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

T;T

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.0028

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.65

.;T

MetaRNN

Benign

0.0030

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.55

N;N

MutationTaster

Benign

0.85

P;P

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.44

N;N

REVEL

Benign

0.18

Sift

Benign

0.34

T;T

Sift4G

Benign

0.51

T;T

Polyphen

0.21

B;B

Vest4

0.13

MPC

0.90

ClinPred

0.014

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.34

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