19-9413988-C-T

Position:

• chr19-9413988-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000592904.7(ZNF266):​c.1138G>A​(p.Glu380Lys) 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. 12/18 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: ZNF266 ENST00000592904.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -8.26

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08568901).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF266	NM_001370374.1	c.1138G>A	p.Glu380Lys	missense_variant	11/11	ENST00000592904.7	NP_001357303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF266	ENST00000592904.7	c.1138G>A	p.Glu380Lys	missense_variant	11/11	1	NM_001370374.1	ENSP00000466714	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 12, 2021

The c.937G>A (p.E313K) alteration is located in exon 11 (coding exon 4) of the ZNF266 gene. This alteration results from a G to A substitution at nucleotide position 937, causing the glutamic acid (E) at amino acid position 313 to be replaced by a lysine (K). 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	0.62
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.8
DANN	Benign	0.92
DEOGEN2	Benign	0.016	.;T;T;T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.000020	N
LIST_S2	Benign	0.51	T;.;.;.;T
M_CAP	Benign	0.00083	T
MetaRNN	Benign	0.086	T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.41	.;N;N;N;N
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.31	T
Sift4G	Benign	0.91	.;T;T;T;T
Polyphen		0.024	.;B;B;B;B
Vest4		0.066, 0.065, 0.067
MutPred		0.31		.;Loss of ubiquitination at K316 (P = 0.0301);Loss of ubiquitination at K316 (P = 0.0301);Loss of ubiquitination at K316 (P = 0.0301);Loss of ubiquitination at K316 (P = 0.0301);
MVP		0.13
MPC		0.034
ClinPred		0.60	D
GERP RS		-4.1
Varity_R		0.032

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: rs2068607555; hg19: chr19-9524664;