19-9413360-C-A

Variant names:

• chr19-9413360-C-A
• rs1329394394
• NM_001370374.1:c.1766G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.83

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]

ACMG classification

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
ZNF266	NM_001370374.1	c.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
ZNF266	ENST00000592904.7	c.1766G>T	p.Cys589Phe	missense_variant	Exon 11 of 11	1	NM_001370374.1	ENSP00000466714.2

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

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

Other links and lift over

dbSNP: rs1329394394; hg19: chr19-9524036;