Variant X-47024894-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The ENST00000614628.5(JADE3):c.455A>G(p.Asn152Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 1,065,052 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000066 ( 0 hom. 3 hem. )

Consequence

JADE3
ENST00000614628.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.85

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 Likely_benign. Variant got -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.893

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JADE3	NM_014735.5 linkuse as main transcript	c.455A>G	p.Asn152Ser	missense_variant	5/11	ENST00000614628.5	NP_055550.1
JADE3	NM_001077445.3 linkuse as main transcript	c.455A>G	p.Asn152Ser	missense_variant	5/11		NP_001070913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
JADE3	ENST00000614628.5 linkuse as main transcript	c.455A>G	p.Asn152Ser	missense_variant	5/11	1	NM_014735.5	ENSP00000481850	P1
JADE3	ENST00000611250.4 linkuse as main transcript	c.455A>G	p.Asn152Ser	missense_variant	5/11	2		ENSP00000479377	P1
JADE3	ENST00000424392.5 linkuse as main transcript	c.455A>G	p.Asn152Ser	missense_variant	5/6	3		ENSP00000391009

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000579

AC:

AN:

172737

Hom.:

AF XY:

0.0000172

AC XY:

AN XY:

58111

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000128

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000657

AC:

AN:

1065052

Hom.:

Cov.:

AF XY:

0.00000901

AC XY:

AN XY:

332978

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000735

Gnomad4 OTH exome

AF:

0.0000222

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

Dec 27, 2022

The c.455A>G (p.N152S) alteration is located in exon 5 (coding exon 4) of the JADE3 gene. This alteration results from a A to G substitution at nucleotide position 455, causing the asparagine (N) at amino acid position 152 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

Uncertain

0.39

BayesDel_addAF

Benign

-0.029

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.50

.;T;T

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D;.

M_CAP

Pathogenic

0.49

MetaRNN

Pathogenic

0.89

D;D;D

MetaSVM

Uncertain

0.0039

MutationAssessor

Pathogenic

3.1

.;M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.48

PROVEAN

Pathogenic

-5.0

D;.;.

REVEL

Uncertain

0.59

Sift

Pathogenic

0.0

D;.;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.86, 0.86

MutPred

0.76

Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);

MVP

0.81

ClinPred

0.98

GERP RS

6.0

Varity_R

0.87

gMVP

0.92

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