19-9413360-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001370374.1(ZNF266):​c.1766G>T​(p.Cys589Phe) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C589R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

ZNF266
NM_001370374.1 missense

Scores

3
6
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.83
Variant links:
Genes affected
ZNF266 (HGNC:13059): (zinc finger protein 266) This gene encodes a protein containing many tandem zinc-finger motifs. Zinc fingers are protein or nucleic acid-binding domains, and may be involved in a variety of functions, including regulation of transcription. This gene is located in a cluster of similar genes encoding zinc finger proteins on chromosome 19. Alternative splicing results in multiple transcript variants for this gene. [provided by RefSeq, Sep 2012]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.748

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF266NM_001370374.1 linkc.1766G>T p.Cys589Phe missense_variant Exon 11 of 11 ENST00000592904.7 NP_001357303.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF266ENST00000592904.7 linkc.1766G>T p.Cys589Phe missense_variant Exon 11 of 11 1 NM_001370374.1 ENSP00000466714.2 A0A3F2YPB8

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 21, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1565G>T (p.C522F) alteration is located in exon 11 (coding exon 4) of the ZNF266 gene. This alteration results from a G to T substitution at nucleotide position 1565, causing the cysteine (C) at amino acid position 522 to be replaced by a phenylalanine (F). 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
Pathogenic
0.83
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
-0.080
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.37
.;T;T;T;T
Eigen
Uncertain
0.45
Eigen_PC
Benign
0.18
FATHMM_MKL
Benign
0.0083
N
LIST_S2
Benign
0.13
T;.;.;.;T
M_CAP
Benign
0.0050
T
MetaRNN
Pathogenic
0.75
D;D;D;D;D
MetaSVM
Uncertain
0.13
D
MutationAssessor
Pathogenic
4.0
.;H;H;H;H
PrimateAI
Benign
0.39
T
Sift4G
Uncertain
0.0060
.;D;D;D;D
Polyphen
1.0
.;D;D;D;D
Vest4
0.41, 0.41, 0.41
MutPred
0.66
.;Loss of ubiquitination at K523 (P = 0.077);Loss of ubiquitination at K523 (P = 0.077);Loss of ubiquitination at K523 (P = 0.077);Loss of ubiquitination at K523 (P = 0.077);
MVP
0.87
MPC
0.25
ClinPred
0.97
D
GERP RS
2.4
Varity_R
0.92

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1329394394; hg19: chr19-9524036; API