Variant X-46984913-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000614628.5(JADE3):c.19G>A(p.Val7Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000315 in 1,207,440 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 21 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000034 ( 0 hom. 21 hem. )

Consequence

JADE3
ENST00000614628.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.646

Variant links:

Genes affected

JADE3 (HGNC:22982): (jade family PHD finger 3) This gene encodes a member of a family of large proteins containing PHD (plant homeo domain)-type zinc fingers. The encoded protein may be associated in a nuclear complex that functions in histone H4 acetylation. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Aug 2013]

JADE3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02161339).

BS2

High Hemizygotes in GnomAdExome4 at 21 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JADE3	NM_014735.5 linkuse as main transcript	c.19G>A	p.Val7Ile	missense_variant	2/11	ENST00000614628.5	NP_055550.1
JADE3	NM_001077445.3 linkuse as main transcript	c.19G>A	p.Val7Ile	missense_variant	2/11		NP_001070913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
JADE3	ENST00000614628.5 linkuse as main transcript	c.19G>A	p.Val7Ile	missense_variant	2/11	1	NM_014735.5	ENSP00000481850	P1
JADE3	ENST00000611250.4 linkuse as main transcript	c.19G>A	p.Val7Ile	missense_variant	2/11	2		ENSP00000479377	P1
JADE3	ENST00000424392.5 linkuse as main transcript	c.19G>A	p.Val7Ile	missense_variant	2/6	3		ENSP00000391009
JADE3	ENST00000455411.1 linkuse as main transcript	c.19G>A	p.Val7Ile	missense_variant	2/5	4		ENSP00000400584

Frequencies

GnomAD3 genomes

AF:

0.00000895

AC:

AN:

111678

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33874

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000374

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000546

AC:

AN:

183213

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

67713

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000525

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000338

AC:

AN:

1095762

Hom.:

Cov.:

AF XY:

0.0000581

AC XY:

AN XY:

361180

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:

0.000647

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000435

GnomAD4 genome

AF:

0.00000895

AC:

AN:

111678

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33874

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000374

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000659

AC:

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

May 20, 2024

The c.19G>A (p.V7I) alteration is located in exon 2 (coding exon 1) of the JADE3 gene. This alteration results from a G to A substitution at nucleotide position 19, causing the valine (V) at amino acid position 7 to be replaced by an isoleucine (I). 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

Benign

0.069

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.38

DANN

Benign

0.72

DEOGEN2

Benign

0.059

.;T;T;T

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.55

T;T;.;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.022

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

.;N;N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.14

N;.;.;N

REVEL

Benign

0.022

Sift

Benign

0.56

T;.;.;T

Sift4G

Benign

0.40

T;T;T;T

Polyphen

0.0

.;B;B;.

Vest4

0.036, 0.033

MutPred

0.16

Gain of methylation at K2 (P = 0.103);Gain of methylation at K2 (P = 0.103);Gain of methylation at K2 (P = 0.103);Gain of methylation at K2 (P = 0.103);

MVP

0.068

ClinPred

0.0073

GERP RS

-2.4

Varity_R

0.036

gMVP

0.11

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