Variant 15-84799209-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_014630.3(ZNF592):c.3136G>A(p.Gly1046Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,614,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

ZNF592
NM_014630.3 missense, splice_region

Scores

Splicing: ADA: 0.7041

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 2.65

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:

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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=0.2516362).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF592	NM_014630.3 linkuse as main transcript	c.3136G>A	p.Gly1046Arg	missense_variant, splice_region_variant	9/11	ENST00000560079.7	NP_055445.2
ZNF592	XM_005254996.4 linkuse as main transcript	c.3136G>A	p.Gly1046Arg	missense_variant, splice_region_variant	8/10		XP_005255053.1
ZNF592	XM_011522246.3 linkuse as main transcript	c.3136G>A	p.Gly1046Arg	missense_variant, splice_region_variant	9/11		XP_011520548.1
ZNF592	XM_011522247.3 linkuse as main transcript	c.3136G>A	p.Gly1046Arg	missense_variant, splice_region_variant	8/10		XP_011520549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF592	ENST00000560079.7 linkuse as main transcript	c.3136G>A	p.Gly1046Arg	missense_variant, splice_region_variant	9/11	1	NM_014630.3	ENSP00000452877	P1
ZNF592	ENST00000559607.1 linkuse as main transcript	c.*548G>A		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	7/9	1		ENSP00000453491
ZNF592	ENST00000299927.4 linkuse as main transcript	c.3136G>A	p.Gly1046Arg	missense_variant, splice_region_variant	6/8	2		ENSP00000299927	P1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000127

AC:

AN:

251438

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000229

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000103

AC:

150

AN:

1461830

Hom.:

Cov.:

AF XY:

0.000106

AC XY:

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000108

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000140

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Galloway-Mowat syndrome 1

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Jun 29, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

T;T

Eigen

Benign

-0.073

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.76

.;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.46

N;N

MutationTaster

Benign

0.82

A;A

PrimateAI

Uncertain

0.67

PROVEAN

Benign

0.74

N;N

REVEL

Benign

0.17

Sift

Benign

0.16

T;T

Sift4G

Benign

0.42

T;T

Polyphen

0.36

B;B

Vest4

0.60

MutPred

0.24

Gain of disorder (P = 0.0398);Gain of disorder (P = 0.0398);

MVP

0.65

MPC

0.39

ClinPred

0.027

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.055

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.70

dbscSNV1_RF

Benign

0.42

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