Variant 15-84784836-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014630.3(ZNF592):c.2161C>T(p.Arg721Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ZNF592
NM_014630.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.912

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29291835).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF592	NM_014630.3 linkuse as main transcript	c.2161C>T	p.Arg721Trp	missense_variant	4/11	ENST00000560079.7	NP_055445.2	Q92610
ZNF592	XM_005254996.4 linkuse as main transcript	c.2161C>T	p.Arg721Trp	missense_variant	3/10		XP_005255053.1	Q92610
ZNF592	XM_011522246.3 linkuse as main transcript	c.2161C>T	p.Arg721Trp	missense_variant	4/11		XP_011520548.1	Q92610
ZNF592	XM_011522247.3 linkuse as main transcript	c.2161C>T	p.Arg721Trp	missense_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.2161C>T	p.Arg721Trp	missense_variant	4/11	1	NM_014630.3	ENSP00000452877.2	Q92610
ZNF592	ENST00000559607.1 linkuse as main transcript	n.2161C>T		non_coding_transcript_exon_variant	2/9	1		ENSP00000453491.1	H0YM74
ZNF592	ENST00000299927.4 linkuse as main transcript	c.2161C>T	p.Arg721Trp	missense_variant	1/8	2		ENSP00000299927.3	Q92610

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251436

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Galloway-Mowat syndrome 1

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Aug 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.057

T;T

Eigen

Benign

-0.047

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.26

LIST_S2

Uncertain

0.93

.;D

M_CAP

Benign

0.028

MetaRNN

Benign

0.29

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;M

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-2.5

N;N

REVEL

Benign

0.17

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.99

D;D

Vest4

0.50

MutPred

0.57

Gain of catalytic residue at M724 (P = 0.0055);Gain of catalytic residue at M724 (P = 0.0055);

MVP

0.068

MPC

0.70

ClinPred

0.61

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.093

gMVP

0.41

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