chr19-9413360-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370374.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF266	NM_001370374.1	MANE Select	c.1766G>T	p.Cys589Phe	missense	Exon 11 of 11	NP_001357303.1	A0A3F2YPB8
	ZNF266	NM_001370375.1		c.1766G>T	p.Cys589Phe	missense	Exon 11 of 11	NP_001357304.1	A0A3F2YPB8
	ZNF266	NM_001370384.1		c.1766G>T	p.Cys589Phe	missense	Exon 10 of 10	NP_001357313.1	A0A3F2YPB8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF266	ENST00000592904.7	TSL:1 MANE Select	c.1766G>T	p.Cys589Phe	missense	Exon 11 of 11	ENSP00000466714.2	A0A3F2YPB8
	ZNF266	ENST00000588933.5	TSL:1	c.1565G>T	p.Cys522Phe	missense	Exon 11 of 11	ENSP00000467151.1	Q14584
	ZNF266	ENST00000590306.5	TSL:1	c.1565G>T	p.Cys522Phe	missense	Exon 10 of 10	ENSP00000467315.1	Q14584

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.45
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.0083	N
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.0050	T
MetaRNN	Pathogenic	0.75	D
MetaSVM	Uncertain	0.13	D
MutationAssessor	Pathogenic	4.0	H
PhyloP100		2.8
PrimateAI	Benign	0.39	T
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.41
MutPred		0.66		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
Mutation Taster		=92/8	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

Other links and lift over

dbSNP: rs1329394394; hg19: chr19-9524036;