chr15-84782941-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014630.3(ZNF592):​c.266G>A​(p.Ser89Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,614,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZNF592
NM_014630.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.29
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.027381986).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZNF592NM_014630.3 linkuse as main transcriptc.266G>A p.Ser89Asn missense_variant 4/11 ENST00000560079.7
ZNF592XM_005254996.4 linkuse as main transcriptc.266G>A p.Ser89Asn missense_variant 3/10
ZNF592XM_011522246.3 linkuse as main transcriptc.266G>A p.Ser89Asn missense_variant 4/11
ZNF592XM_011522247.3 linkuse as main transcriptc.266G>A p.Ser89Asn missense_variant 3/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZNF592ENST00000560079.7 linkuse as main transcriptc.266G>A p.Ser89Asn missense_variant 4/111 NM_014630.3 P1
ZNF592ENST00000559607.1 linkuse as main transcriptc.266G>A p.Ser89Asn missense_variant, NMD_transcript_variant 2/91
ZNF592ENST00000299927.4 linkuse as main transcriptc.266G>A p.Ser89Asn missense_variant 1/82 P1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152180
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000458
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
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
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251490
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135916
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461890
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152298
Hom.:
0
Cov.:
32
AF XY:
0.0000671
AC XY:
5
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000457
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000793

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 submitterclinical testingAmbry GeneticsAug 02, 2021The c.266G>A (p.S89N) alteration is located in exon 4 (coding exon 1) of the ZNF592 gene. This alteration results from a G to A substitution at nucleotide position 266, causing the serine (S) at amino acid position 89 to be replaced by an asparagine (N). 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
0.12
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
20
DANN
Benign
0.92
DEOGEN2
Benign
0.015
T;T
Eigen
Benign
-0.82
Eigen_PC
Benign
-0.58
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.60
.;T
M_CAP
Benign
0.0050
T
MetaRNN
Benign
0.027
T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
-0.90
N;N
MutationTaster
Benign
0.99
N;N
PrimateAI
Benign
0.47
T
PROVEAN
Benign
0.10
N;N
REVEL
Benign
0.10
Sift
Benign
0.76
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0
B;B
Vest4
0.24
MVP
0.068
MPC
0.25
ClinPred
0.091
T
GERP RS
3.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.045
gMVP
0.23

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.

Other links and lift over

dbSNP: rs201486461; hg19: chr15-85326172; API