Variant chr19-36514328-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001166037.2(ZNF260):c.911A>G(p.Tyr304Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000219 in 1,461,804 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000022 ( 1 hom. )

Consequence

ZNF260
NM_001166037.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.599

Variant links:

Genes affected

ZNF260 (HGNC:13499): (zinc finger protein 260) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF260 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF260	NM_001166037.2 linkuse as main transcript	c.911A>G	p.Tyr304Cys	missense_variant	3/3	ENST00000523638.6	NP_001159509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF260	ENST00000523638.6 linkuse as main transcript	c.911A>G	p.Tyr304Cys	missense_variant	3/3	2	NM_001166037.2	ENSP00000429803	P1
ZNF260	ENST00000588993.1 linkuse as main transcript	c.911A>G	p.Tyr304Cys	missense_variant	3/3	1		ENSP00000467219	P1
ZNF260	ENST00000592282.1 linkuse as main transcript	c.911A>G	p.Tyr304Cys	missense_variant	4/4	1		ENSP00000464964	P1
ZNF260	ENST00000593142.5 linkuse as main transcript	c.911A>G	p.Tyr304Cys	missense_variant	2/2	1		ENSP00000465834	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

251346

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1461804

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 26, 2023

The c.911A>G (p.Y304C) alteration is located in exon 4 (coding exon 1) of the ZNF260 gene. This alteration results from a A to G substitution at nucleotide position 911, causing the tyrosine (Y) at amino acid position 304 to be replaced by a cysteine (C). 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

0.60

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;T;T;T

Eigen

Benign

0.14

Eigen_PC

Benign

-0.017

FATHMM_MKL

Benign

0.0059

LIST_S2

Benign

0.098

.;.;.;T

M_CAP

Benign

0.025

MetaRNN

Uncertain

0.43

T;T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.6

M;M;M;M

MutationTaster

Benign

0.62

N;N;N;N

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-7.9

D;.;.;.

REVEL

Benign

0.098

Sift

Uncertain

0.0050

D;.;.;.

Sift4G

Pathogenic

0.0010

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.24

MutPred

0.66

Gain of ubiquitination at K302 (P = 0.0509);Gain of ubiquitination at K302 (P = 0.0509);Gain of ubiquitination at K302 (P = 0.0509);Gain of ubiquitination at K302 (P = 0.0509);

MVP

0.69

MPC

0.58

ClinPred

0.68

GERP RS

2.4

Varity_R

0.35

gMVP

0.19

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