16-3115898-C-T

Variant summary

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

The NM_001042428.2(ZNF205):​c.341C>T​(p.Ala114Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000316 in 1,613,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.000034 ( 0 hom. )

Consequence

ZNF205
NM_001042428.2 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.08

Publications

0 publications found
Variant links:
Genes affected
ZNF205 (HGNC:12996): (zinc finger protein 205) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II; positive regulation of hydrogen peroxide biosynthetic process; and positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway. Predicted to be located in mitochondrion and nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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=0.23157069).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF205NM_001042428.2 linkc.341C>T p.Ala114Val missense_variant Exon 4 of 7 ENST00000219091.9 NP_001035893.1 O95201

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF205ENST00000219091.9 linkc.341C>T p.Ala114Val missense_variant Exon 4 of 7 5 NM_001042428.2 ENSP00000219091.4 O95201

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152278
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000403
AC:
10
AN:
248300
AF XY:
0.0000297
show subpopulations
Gnomad AFR exome
AF:
0.0000622
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000545
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000539
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000335
AC:
49
AN:
1461516
Hom.:
0
Cov.:
31
AF XY:
0.0000289
AC XY:
21
AN XY:
727054
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33476
American (AMR)
AF:
0.00
AC:
0
AN:
44702
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26112
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39690
South Asian (SAS)
AF:
0.0000348
AC:
3
AN:
86208
European-Finnish (FIN)
AF:
0.0000188
AC:
1
AN:
53290
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5744
European-Non Finnish (NFE)
AF:
0.0000387
AC:
43
AN:
1111922
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60372
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.453
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

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:
152278
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74392
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
41476
American (AMR)
AF:
0.00
AC:
0
AN:
15294
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5204
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4832
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:
0.0000294
AC:
2
AN:
68050
Other (OTH)
AF:
0.00
AC:
0
AN:
2094
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.002339), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.350
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.0000847
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.0000330
AC:
4

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 07, 2022
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.341C>T (p.A114V) alteration is located in exon 4 (coding exon 3) of the ZNF205 gene. This alteration results from a C to T substitution at nucleotide position 341, causing the alanine (A) at amino acid position 114 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
AlphaMissense
Benign
0.26
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.22
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.051
T;T;T;.;.
Eigen
Uncertain
0.22
Eigen_PC
Benign
0.097
FATHMM_MKL
Benign
0.51
D
LIST_S2
Benign
0.060
.;.;T;T;T
M_CAP
Benign
0.039
D
MetaRNN
Benign
0.23
T;T;T;T;T
MetaSVM
Benign
-0.43
T
MutationAssessor
Uncertain
2.2
M;M;M;.;.
PhyloP100
4.1
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-1.3
N;N;.;D;D
REVEL
Benign
0.20
Sift
Benign
0.062
T;T;.;D;D
Sift4G
Benign
0.12
T;T;T;D;T
Polyphen
1.0
D;D;D;.;.
Vest4
0.54
MutPred
0.46
Loss of disorder (P = 0.0867);Loss of disorder (P = 0.0867);Loss of disorder (P = 0.0867);Loss of disorder (P = 0.0867);Loss of disorder (P = 0.0867);
MVP
0.81
MPC
0.49
ClinPred
0.39
T
GERP RS
5.2
PromoterAI
-0.040
Neutral
Varity_R
0.11
gMVP
0.17
Mutation Taster
=74/26
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs770380526; hg19: chr16-3165899; COSMIC: COSV54620873; COSMIC: COSV54620873; API