Variant 19-36514349-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001166037.2(ZNF260):c.890T>C(p.Ile297Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF260
NM_001166037.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.406

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2932876).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF260	NM_001166037.2 linkuse as main transcript	c.890T>C	p.Ile297Thr	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.890T>C	p.Ile297Thr	missense_variant	3/3	2	NM_001166037.2	ENSP00000429803	P1
ZNF260	ENST00000588993.1 linkuse as main transcript	c.890T>C	p.Ile297Thr	missense_variant	3/3	1		ENSP00000467219	P1
ZNF260	ENST00000592282.1 linkuse as main transcript	c.890T>C	p.Ile297Thr	missense_variant	4/4	1		ENSP00000464964	P1
ZNF260	ENST00000593142.5 linkuse as main transcript	c.890T>C	p.Ile297Thr	missense_variant	2/2	1		ENSP00000465834	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461802

Hom.:

Cov.:

AF XY:

0.00000138

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 19, 2023

The c.890T>C (p.I297T) alteration is located in exon 4 (coding exon 1) of the ZNF260 gene. This alteration results from a T to C substitution at nucleotide position 890, causing the isoleucine (I) at amino acid position 297 to be replaced by a threonine (T). 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

0.68

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.21

T;T;T;T

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.0083

LIST_S2

Benign

0.13

.;.;.;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.29

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.30

N;N;N;N

MutationTaster

Benign

0.93

N;N;N;N

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-2.4

N;.;.;.

REVEL

Benign

0.078

Sift

Benign

0.21

T;.;.;.

Sift4G

Benign

0.13

T;T;T;T

Polyphen

0.16

B;B;B;B

Vest4

0.60

MutPred

0.55

Loss of stability (P = 0.0049);Loss of stability (P = 0.0049);Loss of stability (P = 0.0049);Loss of stability (P = 0.0049);

MVP

0.48

MPC

0.27

ClinPred

0.14

GERP RS

2.4

Varity_R

0.074

gMVP

0.026

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over