Variant 22-22488462-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_080764.4(ZNF280B):c.937G>A(p.Val313Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,613,856 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0028 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 14 hom. )

Consequence

ZNF280B
NM_080764.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.231

Variant links:

Genes affected

ZNF280B (HGNC:23022): (zinc finger protein 280B) The protein encoded by this gene is a transcription factor that upregulates expression of MDM2, which negatively regulates p53 expression. This gene is highly expressed in prostate cancer cells, which leads to a reduction in p53 levels and an increase in growth of the cancer cells. Several transcript variants have been found for this gene, but only one of them is protein-coding. [provided by RefSeq, Jan 2015]

ZNF280B links:

ZNF280B (HGNC:):

ZNF280B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009470135).

BP6

Variant 22-22488462-C-T is Benign according to our data. Variant chr22-22488462-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2628004.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF280B	NM_080764.4 linkuse as main transcript	c.937G>A	p.Val313Met	missense_variant	4/4	ENST00000626650.3	NP_542942.2	Q86YH2A0A0D9SEJ8B3KUN2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF280B	ENST00000626650.3 linkuse as main transcript	c.937G>A	p.Val313Met	missense_variant	4/4	2	NM_080764.4	ENSP00000485750.1	A0A0D9SEJ8
ZNF280B	ENST00000619852.2 linkuse as main transcript	n.937G>A		non_coding_transcript_exon_variant	4/5	1		ENSP00000480958.1	Q86YH2
ZNF280B	ENST00000613655.1 linkuse as main transcript	c.937G>A	p.Val313Met	missense_variant	1/2	5		ENSP00000481008.1	Q86YH2

Frequencies

GnomAD3 genomes

AF:

0.00276

AC:

419

AN:

151900

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000722

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00971

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00423

Gnomad OTH

AF:

0.000481

GnomAD3 exomes

AF:

0.00230

AC:

578

AN:

251388

Hom.:

AF XY:

0.00227

AC XY:

308

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00397

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00831

Gnomad NFE exome

AF:

0.00288

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00176

AC:

2568

AN:

1461838

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

1357

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.00352

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00895

Gnomad4 NFE exome

AF:

0.00168

Gnomad4 OTH exome

AF:

0.00179

GnomAD4 genome

AF:

0.00276

AC:

419

AN:

152018

Hom.:

Cov.:

AF XY:

0.00308

AC XY:

229

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000721

Gnomad4 ASJ

AF:

0.00260

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00971

Gnomad4 NFE

AF:

0.00424

Gnomad4 OTH

AF:

0.000476

Alfa

AF:

0.00374

Hom.:

Bravo

AF:

0.00115

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00256

AC:

ExAC

AF:

0.00243

AC:

295

EpiCase

AF:

0.00207

EpiControl

AF:

0.00136

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Exstrophy-epispadias complex

Uncertain:1

Uncertain significance, criteria provided, single submitter

curation

Obstetrics and Gynecology Department, Johns Hopkins School Of Medicine

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

ZNF280B: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.58

CADD

Benign

9.9

DANN

Benign

0.94

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.80

.;T

M_CAP

Benign

0.0021

MetaRNN

Benign

0.0095

T;T

MetaSVM

Benign

-0.95

PrimateAI

Benign

0.38

Sift4G

Benign

0.064

T;T

Vest4

0.094

MVP

0.12

ClinPred

0.014

GERP RS

-1.2

gMVP

0.20

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