rs774105754

Variant summary

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

The NM_004220.3(ZNF213):​c.404T>C​(p.Val135Ala) 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 1,613,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

ZNF213
NM_004220.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0100

Publications

0 publications found
Variant links:
Genes affected
ZNF213 (HGNC:13005): (zinc finger protein 213) C2H2 zinc finger proteins, such as ZNF213, have bipartite structures in which one domain binds DNA or RNA and the other modulates target gene expression.[supplied by OMIM, Apr 2004]
ZNF213-AS1 (HGNC:50505): (ZNF213 antisense RNA 1 (head to head))

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=0.070020705).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF213NM_004220.3 linkc.404T>C p.Val135Ala missense_variant Exon 3 of 6 ENST00000396878.8 NP_004211.1 O14771-1A0A0S2Z4L6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF213ENST00000396878.8 linkc.404T>C p.Val135Ala missense_variant Exon 3 of 6 1 NM_004220.3 ENSP00000380087.3 O14771-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152224
Hom.:
0
Cov.:
33
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:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000243
AC:
6
AN:
247036
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:
0.000220
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000181
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461180
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
726896
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33454
American (AMR)
AF:
0.00
AC:
0
AN:
44624
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26100
East Asian (EAS)
AF:
0.0000756
AC:
3
AN:
39682
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86200
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53336
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5720
European-Non Finnish (NFE)
AF:
0.00000540
AC:
6
AN:
1111708
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60356
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
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:
0.0000131
AC:
2
AN:
152224
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74362
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41468
American (AMR)
AF:
0.00
AC:
0
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.000192
AC:
1
AN:
5204
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10628
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
68016
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.450
Heterozygous variant carriers
0
0
1
1
2
2
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:
0.00
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 03, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.404T>C (p.V135A) alteration is located in exon 3 (coding exon 2) of the ZNF213 gene. This alteration results from a T to C substitution at nucleotide position 404, causing the valine (V) at amino acid position 135 to be replaced by an alanine (A). 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
0.13
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
16
DANN
Benign
0.76
DEOGEN2
Benign
0.057
T;T;T;T;.;T
Eigen
Benign
-0.49
Eigen_PC
Benign
-0.38
FATHMM_MKL
Benign
0.059
N
LIST_S2
Benign
0.54
.;.;.;T;T;T
M_CAP
Benign
0.0097
T
MetaRNN
Benign
0.070
T;T;T;T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.0
N;N;N;N;.;.
PhyloP100
-0.010
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-1.2
.;N;.;N;.;.
REVEL
Benign
0.042
Sift
Benign
0.12
.;T;.;T;.;.
Sift4G
Benign
0.19
T;T;T;T;T;T
Polyphen
0.14
B;B;B;B;.;.
Vest4
0.23
MutPred
0.65
Gain of relative solvent accessibility (P = 0.1571);Gain of relative solvent accessibility (P = 0.1571);Gain of relative solvent accessibility (P = 0.1571);Gain of relative solvent accessibility (P = 0.1571);.;.;
MVP
0.50
MPC
0.25
ClinPred
0.054
T
GERP RS
1.7
Varity_R
0.045
gMVP
0.27
Mutation Taster
=86/14
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: rs774105754; hg19: chr16-3188423; API