Variant 5-134559913-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001388185.1(JADE2):c.395C>T(p.Pro132Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,613,994 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0075 ( 13 hom., cov: 33)

Exomes 𝑓: 0.00074 ( 9 hom. )

Consequence

JADE2
NM_001388185.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.76

Variant links:

Genes affected

JADE2 (HGNC:22984): (jade family PHD finger 2) Predicted to enable ubiquitin protein ligase activity. Involved in histone acetylation. Located in nucleoplasm. Part of histone acetyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]

JADE2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003025204).

BP6

Variant 5-134559913-C-T is Benign according to our data. Variant chr5-134559913-C-T is described in ClinVar as [Benign]. Clinvar id is 783447.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00752 (1145/152354) while in subpopulation AFR AF= 0.0267 (1111/41576). AF 95% confidence interval is 0.0254. There are 13 homozygotes in gnomad4. There are 547 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JADE2	NM_001388185.1 linkuse as main transcript	c.395C>T	p.Pro132Leu	missense_variant	5/12	ENST00000681547.2	NP_001375114.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JADE2	ENST00000681547.2 linkuse as main transcript	c.395C>T	p.Pro132Leu	missense_variant	5/12		NM_001388185.1	ENSP00000505514	A1

Frequencies

GnomAD3 genomes

AF:

0.00749

AC:

1141

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0267

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00195

AC:

489

AN:

250502

Hom.:

AF XY:

0.00142

AC XY:

193

AN XY:

135568

show subpopulations

Gnomad AFR exome

AF:

0.0277

Gnomad AMR exome

AF:

0.000871

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.000743

AC:

1086

AN:

1461640

Hom.:

Cov.:

AF XY:

0.000631

AC XY:

459

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.0281

Gnomad4 AMR exome

AF:

0.000806

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.00142

GnomAD4 genome

AF:

0.00752

AC:

1145

AN:

152354

Hom.:

Cov.:

AF XY:

0.00734

AC XY:

547

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.0267

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00101

Hom.:

Bravo

AF:

0.00846

ESP6500AA

AF:

0.0288

AC:

127

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00259

AC:

314

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

T;T;T;T;T;T

Eigen

Benign

-0.086

Eigen_PC

Benign

0.11

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.84

T;T;T;T;T;T

MetaRNN

Benign

0.0030

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

.;.;.;.;N;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.86

N;N;N;N;N;N

REVEL

Benign

0.028

Sift

Benign

0.28

T;T;T;T;T;T

Sift4G

Benign

0.32

T;T;T;T;T;T

Polyphen

0.0010, 0.018

.;.;.;B;B;.

Vest4

0.40, 0.36, 0.41, 0.36

MVP

0.14

MPC

0.85

ClinPred

0.0085

GERP RS

4.2

Varity_R

0.043

gMVP

0.41

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