chr16-3115850-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001042428.2(ZNF205):​c.293C>T​(p.Pro98Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

ZNF205
NM_001042428.2 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.931

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))

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.33357316).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF205NM_001042428.2 linkc.293C>T p.Pro98Leu 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.293C>T p.Pro98Leu missense_variant Exon 4 of 7 5 NM_001042428.2 ENSP00000219091.4 O95201

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 19, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.293C>T (p.P98L) 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 293, causing the proline (P) at amino acid position 98 to be replaced by a leucine (L). 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
-0.068
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.22
T;T;T;.;.
Eigen
Benign
-0.021
Eigen_PC
Benign
-0.17
FATHMM_MKL
Benign
0.21
N
LIST_S2
Benign
0.74
.;.;T;T;T
M_CAP
Benign
0.045
D
MetaRNN
Benign
0.33
T;T;T;T;T
MetaSVM
Benign
-0.75
T
MutationAssessor
Uncertain
2.1
M;M;M;.;.
PhyloP100
0.93
PrimateAI
Benign
0.38
T
PROVEAN
Uncertain
-3.7
D;D;.;D;D
REVEL
Benign
0.16
Sift
Benign
0.046
D;D;.;T;T
Sift4G
Benign
0.069
T;T;T;T;T
Polyphen
0.99
D;D;D;.;.
Vest4
0.28
MutPred
0.45
Loss of disorder (P = 0.0149);Loss of disorder (P = 0.0149);Loss of disorder (P = 0.0149);Loss of disorder (P = 0.0149);Loss of disorder (P = 0.0149);
MVP
0.83
MPC
0.15
ClinPred
0.95
D
GERP RS
5.2
PromoterAI
0.024
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.10
gMVP
0.47

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: rs770667015; hg19: chr16-3165851; API