Variant 19-36514818-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001166037.2(ZNF260):c.421T>A(p.Cys141Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 7.10

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.8

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF260	NM_001166037.2 linkuse as main transcript	c.421T>A	p.Cys141Ser	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.421T>A	p.Cys141Ser	missense_variant	3/3	2	NM_001166037.2	ENSP00000429803	P1
ZNF260	ENST00000588993.1 linkuse as main transcript	c.421T>A	p.Cys141Ser	missense_variant	3/3	1		ENSP00000467219	P1
ZNF260	ENST00000592282.1 linkuse as main transcript	c.421T>A	p.Cys141Ser	missense_variant	4/4	1		ENSP00000464964	P1
ZNF260	ENST00000593142.5 linkuse as main transcript	c.421T>A	p.Cys141Ser	missense_variant	2/2	1		ENSP00000465834	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461730

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

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

Sep 26, 2023

The c.421T>A (p.C141S) alteration is located in exon 4 (coding exon 1) of the ZNF260 gene. This alteration results from a T to A substitution at nucleotide position 421, causing the cysteine (C) at amino acid position 141 to be replaced by a serine (S). 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

0.87

BayesDel_addAF

Pathogenic

0.44

BayesDel_noAF

Pathogenic

0.39

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.47

T;T;T;T

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.12

.;.;.;T

M_CAP

Uncertain

0.25

MetaRNN

Pathogenic

0.80

D;D;D;D

MetaSVM

Uncertain

0.76

MutationAssessor

Pathogenic

4.0

H;H;H;H

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-9.6

D;.;.;.

REVEL

Pathogenic

0.77

Sift

Pathogenic

0.0

D;.;.;.

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.49

MutPred

0.76

Gain of disorder (P = 0.0319);Gain of disorder (P = 0.0319);Gain of disorder (P = 0.0319);Gain of disorder (P = 0.0319);

MVP

0.87

MPC

0.58

ClinPred

1.0

GERP RS

3.8

Varity_R

0.85

gMVP

0.094

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