Variant 19-11487712-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000293771.10(ZNF653):c.751G>A(p.Val251Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00546 in 1,613,744 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0042 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0056 ( 29 hom. )

Consequence

ZNF653
ENST00000293771.10 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.887

Variant links:

Genes affected

ZNF653 (HGNC:25196): (zinc finger protein 653) Enables AF-2 domain binding activity and transcription corepressor activity. Involved in extracellular negative regulation of signal transduction and negative regulation of nucleic acid-templated transcription. Predicted to be located in extracellular region. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF653 links:

ENSG00000267477 (HGNC:):

ENSG00000267477 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005102366).

BP6

Variant 19-11487712-C-T is Benign according to our data. Variant chr19-11487712-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2649332.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF653	NM_138783.4 linkuse as main transcript	c.751G>A	p.Val251Met	missense_variant	4/9	ENST00000293771.10	NP_620138.2	Q96CK0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF653	ENST00000293771.10 linkuse as main transcript	c.751G>A	p.Val251Met	missense_variant	4/9	1	NM_138783.4	ENSP00000293771.3	Q96CK0
ENSG00000267477	ENST00000585656.1 linkuse as main transcript	n.469+8238G>A		intron_variant		5		ENSP00000466387.1	K7EM74
ZNF653	ENST00000590548.5 linkuse as main transcript	n.786G>A		non_coding_transcript_exon_variant	4/8	2

Frequencies

GnomAD3 genomes

AF:

0.00418

AC:

636

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00328

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00358

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00613

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00427

AC:

1067

AN:

250038

Hom.:

AF XY:

0.00437

AC XY:

592

AN XY:

135540

show subpopulations

Gnomad AFR exome

AF:

0.00291

Gnomad AMR exome

AF:

0.00191

Gnomad ASJ exome

AF:

0.0000996

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00252

Gnomad FIN exome

AF:

0.00467

Gnomad NFE exome

AF:

0.00665

Gnomad OTH exome

AF:

0.00426

GnomAD4 exome

AF:

0.00559

AC:

8173

AN:

1461392

Hom.:

Cov.:

AF XY:

0.00565

AC XY:

4105

AN XY:

727028

show subpopulations

Gnomad4 AFR exome

AF:

0.00379

Gnomad4 AMR exome

AF:

0.00208

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00248

Gnomad4 FIN exome

AF:

0.00524

Gnomad4 NFE exome

AF:

0.00646

Gnomad4 OTH exome

AF:

0.00427

GnomAD4 genome

AF:

0.00417

AC:

636

AN:

152352

Hom.:

Cov.:

AF XY:

0.00397

AC XY:

296

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00327

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00248

Gnomad4 FIN

AF:

0.00358

Gnomad4 NFE

AF:

0.00613

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00542

Hom.:

Bravo

AF:

0.00419

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.00386

AC:

ESP6500EA

AF:

0.00535

AC:

ExAC

AF:

0.00450

AC:

546

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

ZNF653: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.023

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.73

M_CAP

Benign

0.0062

MetaRNN

Benign

0.0051

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

MutationTaster

Benign

0.59

PrimateAI

Uncertain

0.58

PROVEAN

Benign

0.24

REVEL

Benign

0.052

Sift

Benign

0.14

Sift4G

Benign

0.10

Polyphen

0.066

Vest4

0.24

MVP

0.34

MPC

0.19

ClinPred

0.0048

GERP RS

3.2

Varity_R

0.065

gMVP

0.26

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