rs186517709

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001076678.3(ZNF493):​c.145C>G​(p.Leu49Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 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: 0.0000034 ( 0 hom. )

Consequence

ZNF493
NM_001076678.3 missense

Scores

4
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.90

Publications

0 publications found
Variant links:
Genes affected
ZNF493 (HGNC:23708): (zinc finger protein 493) Predicted to enable DNA-binding transcription activator 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: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.078888506).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF493NM_001076678.3 linkc.145C>G p.Leu49Val missense_variant Exon 2 of 4 ENST00000392288.7 NP_001070146.1 Q6ZR52-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF493ENST00000392288.7 linkc.145C>G p.Leu49Val missense_variant Exon 2 of 4 1 NM_001076678.3 ENSP00000376110.2 Q6ZR52-2
ENSG00000269237ENST00000600810.1 linkn.85C>G non_coding_transcript_exon_variant Exon 1 of 5 3 ENSP00000473166.1 M0R3E3

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152180
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.000956
GnomAD2 exomes
AF:
0.0000200
AC:
5
AN:
250462
AF XY:
0.0000148
show subpopulations
Gnomad AFR exome
AF:
0.000308
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS 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:
0.00000342
AC:
5
AN:
1460996
Hom.:
0
Cov.:
35
AF XY:
0.00000413
AC XY:
3
AN XY:
726798
show subpopulations
African (AFR)
AF:
0.000150
AC:
5
AN:
33420
American (AMR)
AF:
0.00
AC:
0
AN:
44514
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26088
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39668
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86076
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53350
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111784
Other (OTH)
AF:
0.00
AC:
0
AN:
60332
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.415
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome 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
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152298
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74474
show subpopulations
African (AFR)
AF:
0.000120
AC:
5
AN:
41576
American (AMR)
AF:
0.00
AC:
0
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5194
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10608
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68020
Other (OTH)
AF:
0.000946
AC:
2
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.489
Heterozygous variant carriers
0
1
2
2
3
4
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:
0.0000712
Hom.:
0
Bravo
AF:
0.0000567
ExAC
AF:
0.0000412
AC:
5

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jun 17, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.145C>G (p.L49V) alteration is located in exon 2 (coding exon 2) of the ZNF493 gene. This alteration results from a C to G substitution at nucleotide position 145, causing the leucine (L) at amino acid position 49 to be replaced by a valine (V). 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
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
17
DANN
Uncertain
1.0
Eigen
Benign
-0.26
Eigen_PC
Benign
-0.54
FATHMM_MKL
Benign
0.0050
N
LIST_S2
Benign
0.53
T;T;T;T
M_CAP
Benign
0.0014
T
MetaRNN
Benign
0.079
T;T;T;T
MetaSVM
Benign
-1.1
T
PhyloP100
-1.9
PrimateAI
Benign
0.32
T
PROVEAN
Uncertain
-2.5
.;N;.;D
REVEL
Benign
0.055
Sift
Uncertain
0.0010
.;D;.;D
Sift4G
Uncertain
0.021
D;D;D;D
Polyphen
0.93
.;P;.;.
Vest4
0.20
MVP
0.24
MPC
0.047
ClinPred
0.20
T
GERP RS
1.1
gMVP
0.025
Mutation Taster
=98/2
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: rs186517709; hg19: chr19-21588045; API