NM_001172690.2:c.1529A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001172690.2(ZNF573):​c.1529A>G​(p.His510Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000689 in 1,613,914 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 0.00037 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00072 ( 0 hom. )

Consequence

ZNF573
NM_001172690.2 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -5.28

Publications

1 publications found
Variant links:
Genes affected
ZNF573 (HGNC:26420): (zinc finger protein 573) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.013619959).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF573NM_001172690.2 linkc.1529A>G p.His510Arg missense_variant Exon 5 of 5 ENST00000536220.7 NP_001166161.1 Q86YE8-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF573ENST00000536220.7 linkc.1529A>G p.His510Arg missense_variant Exon 5 of 5 3 NM_001172690.2 ENSP00000440464.2 Q86YE8-1

Frequencies

GnomAD3 genomes
AF:
0.000375
AC:
57
AN:
152160
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000794
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.000506
AC:
127
AN:
251098
AF XY:
0.000567
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000231
Gnomad NFE exome
AF:
0.00103
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000722
AC:
1055
AN:
1461754
Hom.:
0
Cov.:
38
AF XY:
0.000721
AC XY:
524
AN XY:
727172
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33478
American (AMR)
AF:
0.000201
AC:
9
AN:
44718
Ashkenazi Jewish (ASJ)
AF:
0.0000383
AC:
1
AN:
26132
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39684
South Asian (SAS)
AF:
0.0000116
AC:
1
AN:
86244
European-Finnish (FIN)
AF:
0.000319
AC:
17
AN:
53368
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
0.000892
AC:
992
AN:
1111974
Other (OTH)
AF:
0.000580
AC:
35
AN:
60390
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
64
128
193
257
321
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
38
76
114
152
190
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.000375
AC:
57
AN:
152160
Hom.:
0
Cov.:
32
AF XY:
0.000283
AC XY:
21
AN XY:
74330
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41424
American (AMR)
AF:
0.0000654
AC:
1
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5180
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
0.000188
AC:
2
AN:
10618
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.000794
AC:
54
AN:
68038
Other (OTH)
AF:
0.00
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.495
Heterozygous variant carriers
0
3
5
8
10
13
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.000557
Hom.:
0
Bravo
AF:
0.000370
TwinsUK
AF:
0.00162
AC:
6
ALSPAC
AF:
0.00104
AC:
4
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.00116
AC:
10
ExAC
AF:
0.000667
AC:
81
EpiCase
AF:
0.000763
EpiControl
AF:
0.000415

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 10, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.1529A>G (p.H510R) alteration is located in exon 5 (coding exon 4) of the ZNF573 gene. This alteration results from a A to G substitution at nucleotide position 1529, causing the histidine (H) at amino acid position 510 to be replaced by an arginine (R). 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
0.077
BayesDel_addAF
Benign
-0.69
T
BayesDel_noAF
Benign
-0.79
CADD
Benign
0.30
DANN
Benign
0.64
DEOGEN2
Benign
0.0068
T;.;.;T;.
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.023
N
LIST_S2
Benign
0.66
.;T;T;T;T
M_CAP
Benign
0.00058
T
MetaRNN
Benign
0.014
T;T;T;T;T
MetaSVM
Benign
-0.94
T
PhyloP100
-5.3
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-0.57
.;N;N;.;N
REVEL
Benign
0.029
Sift
Benign
0.74
.;T;T;.;T
Sift4G
Benign
0.68
T;T;T;T;T
Polyphen
0.25, 0.15
.;B;B;.;B
Vest4
0.029
MVP
0.061
MPC
0.20
ClinPred
0.024
T
GERP RS
-1.9
Varity_R
0.034
gMVP
0.0081
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs147912292; hg19: chr19-38229862; API