Genetic Variant NM_014630.3:c.548T>C (chr15-84783223-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014630.3(ZNF592):c.548T>C(p.Leu183Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000656 in 152,330 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

ZNF592
NM_014630.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.92

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014630.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF592	NM_014630.3	MANE Select	c.548T>C	p.Leu183Pro	missense	Exon 4 of 11	NP_055445.2	Q92610

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF592	ENST00000560079.7	TSL:1 MANE Select	c.548T>C	p.Leu183Pro	missense	Exon 4 of 11	ENSP00000452877.2	Q92610
ZNF592	ENST00000559607.1	TSL:1	n.548T>C		non_coding_transcript_exon	Exon 2 of 9	ENSP00000453491.1	H0YM74
ZNF592	ENST00000877254.1		c.548T>C	p.Leu183Pro	missense	Exon 2 of 9	ENSP00000547313.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250632

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000656

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41582

American (AMR)

AF:

0.00

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.70

M_CAP

Benign

0.037

MetaRNN

Uncertain

0.46

MetaSVM

Uncertain

-0.27

MutationAssessor

Benign

0.69

PhyloP100

3.9

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.35

REVEL

Benign

0.24

Sift

Uncertain

0.028

Sift4G

Benign

0.13

Polyphen

1.0

Vest4

0.83

MutPred

0.50

Gain of loop (P = 0.0013)

MVP

0.36

MPC

1.2

ClinPred

0.86

GERP RS

6.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.28

gMVP

0.48

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over