Variant 15-84783190-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014630.3(ZNF592):c.515C>T(p.Pro172Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000935 in 1,614,182 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P172R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00056 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00097 ( 3 hom. )

Consequence

ZNF592
NM_014630.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.11

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.064458966).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZNF592	NM_014630.3 linkuse as main transcript	c.515C>T	p.Pro172Leu	missense_variant	4/11	ENST00000560079.7
ZNF592	XM_005254996.4 linkuse as main transcript	c.515C>T	p.Pro172Leu	missense_variant	3/10
ZNF592	XM_011522246.3 linkuse as main transcript	c.515C>T	p.Pro172Leu	missense_variant	4/11
ZNF592	XM_011522247.3 linkuse as main transcript	c.515C>T	p.Pro172Leu	missense_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ZNF592	ENST00000560079.7 linkuse as main transcript	c.515C>T	p.Pro172Leu	missense_variant	4/11	1	NM_014630.3	P1
ZNF592	ENST00000559607.1 linkuse as main transcript	c.515C>T	p.Pro172Leu	missense_variant, NMD_transcript_variant	2/9	1
ZNF592	ENST00000299927.4 linkuse as main transcript	c.515C>T	p.Pro172Leu	missense_variant	1/8	2		P1

Frequencies

GnomAD3 genomes

AF:

0.000565

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00106

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000526

AC:

132

AN:

250752

Hom.:

AF XY:

0.000582

AC XY:

AN XY:

135710

show subpopulations

Gnomad AFR exome

AF:

0.0000623

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000647

Gnomad NFE exome

AF:

0.000874

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000974

AC:

1424

AN:

1461880

Hom.:

Cov.:

AF XY:

0.000932

AC XY:

678

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.000431

Gnomad4 NFE exome

AF:

0.00121

Gnomad4 OTH exome

AF:

0.000447

GnomAD4 genome

AF:

0.000558

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00106

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000287

Hom.:

Bravo

AF:

0.000638

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000601

AC:

EpiCase

AF:

0.00125

EpiControl

AF:

0.00113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 08, 2022

The c.515C>T (p.P172L) alteration is located in exon 4 (coding exon 1) of the ZNF592 gene. This alteration results from a C to T substitution at nucleotide position 515, causing the proline (P) at amino acid position 172 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.055

T;T

Eigen

Benign

0.16

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.77

.;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.064

T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.13

Sift

Benign

0.13

T;T

Sift4G

Uncertain

0.014

D;D

Polyphen

0.88

P;P

Vest4

0.37

MVP

0.11

MPC

0.64

ClinPred

0.043

GERP RS

6.1

Varity_R

0.063

gMVP

0.078

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