Variant rs143880466 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2

The NM_014630.3(ZNF592):c.1618C>T(p.Leu540Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,614,248 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. L540L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 7 hom. )

Consequence

ZNF592
NM_014630.3 synonymous

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 1.99

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP7

Synonymous conserved (PhyloP=1.99 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF592	NM_014630.3 linkuse as main transcript	c.1618C>T	p.Leu540Leu	synonymous_variant	4/11	ENST00000560079.7	NP_055445.2	Q92610
ZNF592	XM_005254996.4 linkuse as main transcript	c.1618C>T	p.Leu540Leu	synonymous_variant	3/10		XP_005255053.1	Q92610
ZNF592	XM_011522246.3 linkuse as main transcript	c.1618C>T	p.Leu540Leu	synonymous_variant	4/11		XP_011520548.1	Q92610
ZNF592	XM_011522247.3 linkuse as main transcript	c.1618C>T	p.Leu540Leu	synonymous_variant	3/10		XP_011520549.1	Q92610

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF592	ENST00000560079.7 linkuse as main transcript	c.1618C>T	p.Leu540Leu	synonymous_variant	4/11	1	NM_014630.3	ENSP00000452877.2	Q92610
ZNF592	ENST00000559607.1 linkuse as main transcript	n.1618C>T		non_coding_transcript_exon_variant	2/9	1		ENSP00000453491.1	H0YM74
ZNF592	ENST00000299927.4 linkuse as main transcript	c.1618C>T	p.Leu540Leu	synonymous_variant	1/8	2		ENSP00000299927.3	Q92610

Frequencies

GnomAD3 genomes

AF:

0.00114

AC:

173

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00461

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000735

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00187

AC:

469

AN:

251328

Hom.:

AF XY:

0.00196

AC XY:

266

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000520

Gnomad ASJ exome

AF:

0.0160

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00245

Gnomad FIN exome

AF:

0.00527

Gnomad NFE exome

AF:

0.000766

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00105

AC:

1531

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

876

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000514

Gnomad4 ASJ exome

AF:

0.0160

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00272

Gnomad4 FIN exome

AF:

0.00477

Gnomad4 NFE exome

AF:

0.000400

Gnomad4 OTH exome

AF:

0.00189

GnomAD4 genome

AF:

0.00114

AC:

173

AN:

152354

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.0124

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.00461

Gnomad4 NFE

AF:

0.000735

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00182

Hom.:

Bravo

AF:

0.000790

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.000889

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jun 27, 2014

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

9.2

DANN

Benign

0.72

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