Variant 15-84783054-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_014630.3(ZNF592):c.379C>A(p.Leu127Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000606 in 1,614,196 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00063 ( 10 hom. )

Consequence

ZNF592
NM_014630.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0610

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033040345).

BP6

Variant 15-84783054-C-A is Benign according to our data. Variant chr15-84783054-C-A is described in ClinVar as [Benign]. Clinvar id is 3043504.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZNF592	NM_014630.3 linkuse as main transcript	c.379C>A	p.Leu127Met	missense_variant	4/11	ENST00000560079.7
ZNF592	XM_005254996.4 linkuse as main transcript	c.379C>A	p.Leu127Met	missense_variant	3/10
ZNF592	XM_011522246.3 linkuse as main transcript	c.379C>A	p.Leu127Met	missense_variant	4/11
ZNF592	XM_011522247.3 linkuse as main transcript	c.379C>A	p.Leu127Met	missense_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ZNF592	ENST00000560079.7 linkuse as main transcript	c.379C>A	p.Leu127Met	missense_variant	4/11	1	NM_014630.3	P1
ZNF592	ENST00000559607.1 linkuse as main transcript	c.379C>A	p.Leu127Met	missense_variant, NMD_transcript_variant	2/9	1
ZNF592	ENST00000299927.4 linkuse as main transcript	c.379C>A	p.Leu127Met	missense_variant	1/8	2		P1

Frequencies

GnomAD3 genomes

AF:

0.000394

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0110

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00114

AC:

287

AN:

251264

Hom.:

AF XY:

0.00161

AC XY:

219

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00915

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000629

AC:

919

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000920

AC XY:

669

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0101

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.000513

GnomAD4 genome

AF:

0.000394

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.000645

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0110

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000110

ExAC

AF:

0.00128

AC:

156

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ZNF592-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 27, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.55

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.013

T;T

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.77

MetaRNN

Benign

0.0033

T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.81

L;L

MutationTaster

Benign

0.74

N;N

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-0.33

N;N

Sift

Benign

0.065

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.99

D;D

Vest4

0.26

MutPred

0.15

Loss of methylation at K126 (P = 0.0396);Loss of methylation at K126 (P = 0.0396);

MVP

0.068

MPC

0.91

ClinPred

0.077

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.087

gMVP

0.14

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