Genetic Variant ZNF266:p.Asn431Tyr (chr19-9413835-T-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001370374.1(ZNF266):c.1291A>T(p.Asn431Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0024 in 1,614,026 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0025 ( 8 hom. )

Consequence

ZNF266
NM_001370374.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.830

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]

ZNF266 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009471148).

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF266	NM_001370374.1 link	c.1291A>T	p.Asn431Tyr	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 link	c.1291A>T	p.Asn431Tyr	missense_variant	Exon 11 of 11	1	NM_001370374.1	ENSP00000466714.2		A0A3F2YPB8

Frequencies

GnomAD3 genomes

AF:

0.00144

AC:

219

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00260

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00135

AC:

339

AN:

250840

Hom.:

AF XY:

0.00146

AC XY:

198

AN XY:

135702

show subpopulations

Gnomad AFR exome

AF:

0.000187

Gnomad AMR exome

AF:

0.000724

Gnomad ASJ exome

AF:

0.0000996

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000741

Gnomad NFE exome

AF:

0.00251

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00251

AC:

3662

AN:

1461768

Hom.:

Cov.:

AF XY:

0.00243

AC XY:

1768

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000649

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000637

Gnomad4 NFE exome

AF:

0.00313

Gnomad4 OTH exome

AF:

0.00167

GnomAD4 genome

AF:

0.00144

AC:

219

AN:

152258

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.00260

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00236

Hom.:

Bravo

AF:

0.00144

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00233

AC:

ExAC

AF:

0.00134

AC:

163

EpiCase

AF:

0.00278

EpiControl

AF:

0.00332

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 12, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1090A>T (p.N364Y) alteration is located in exon 11 (coding exon 4) of the ZNF266 gene. This alteration results from a A to T substitution at nucleotide position 1090, causing the asparagine (N) at amino acid position 364 to be replaced by a tyrosine (Y). 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

0.23

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.4

DANN

Benign

0.94

DEOGEN2

Benign

0.040

.;T;T;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.000020

LIST_S2

Benign

0.17

T;.;.;.;T

M_CAP

Benign

0.00082

MetaRNN

Benign

0.0095

T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.99

.;L;L;L;L

PrimateAI

Benign

0.30

Sift4G

Benign

0.36

.;T;T;T;T

Polyphen

0.0020

.;B;B;B;B

Vest4

0.11, 0.13, 0.13, 0.13

MVP

0.16

MPC

0.032

ClinPred

0.0025

GERP RS

-3.3

Varity_R

0.029

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over