Variant X-46985760-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM1BP4_ModerateBS2

The NM_014735.5(JADE3):c.94A>G(p.Lys32Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00003 in 1,199,153 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000025 ( 0 hom. 10 hem. )

Consequence

JADE3
NM_014735.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.40

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM1

In a modified_residue N6-acetyllysine (size 0) in uniprot entity JADE3_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.07747987).

BS2

High Hemizygotes in GnomAdExome4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JADE3	NM_014735.5 linkuse as main transcript	c.94A>G	p.Lys32Glu	missense_variant	3/11	ENST00000614628.5	NP_055550.1
JADE3	NM_001077445.3 linkuse as main transcript	c.94A>G	p.Lys32Glu	missense_variant	3/11		NP_001070913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
JADE3	ENST00000614628.5 linkuse as main transcript	c.94A>G	p.Lys32Glu	missense_variant	3/11	1	NM_014735.5	ENSP00000481850	P1
JADE3	ENST00000611250.4 linkuse as main transcript	c.94A>G	p.Lys32Glu	missense_variant	3/11	2		ENSP00000479377	P1
JADE3	ENST00000424392.5 linkuse as main transcript	c.94A>G	p.Lys32Glu	missense_variant	3/6	3		ENSP00000391009
JADE3	ENST00000455411.1 linkuse as main transcript	c.94A>G	p.Lys32Glu	missense_variant	3/5	4		ENSP00000400584

Frequencies

GnomAD3 genomes

AF:

0.0000803

AC:

AN:

112021

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

34169

show subpopulations

Gnomad AFR

AF:

0.0000974

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000567

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000110

AC:

AN:

181446

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

66058

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:

0.0000123

Gnomad OTH exome

AF:

0.000223

GnomAD4 exome

AF:

0.0000248

AC:

AN:

1087082

Hom.:

Cov.:

AF XY:

0.0000283

AC XY:

AN XY:

352910

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

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:

0.0000264

Gnomad4 OTH exome

AF:

0.0000875

GnomAD4 genome

AF:

0.0000803

AC:

AN:

112071

Hom.:

Cov.:

AF XY:

0.0000292

AC XY:

AN XY:

34229

show subpopulations

Gnomad4 AFR

AF:

0.0000972

Gnomad4 AMR

AF:

0.000566

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000132

ExAC

AF:

0.0000330

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

Jan 09, 2024

The c.94A>G (p.K32E) alteration is located in exon 3 (coding exon 2) of the JADE3 gene. This alteration results from a A to G substitution at nucleotide position 94, causing the lysine (K) at amino acid position 32 to be replaced by a glutamic acid (E). 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

0.14

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

.;T;T;T

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.77

T;T;.;T

M_CAP

Benign

0.0083

MetaRNN

Benign

0.077

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.4

.;M;M;.

MutationTaster

Benign

0.99

D;D

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.90

N;.;.;N

REVEL

Benign

0.13

Sift

Benign

0.62

T;.;.;T

Sift4G

Benign

0.65

T;T;T;T

Polyphen

0.036

.;B;B;.

Vest4

0.28

MutPred

0.52

Loss of methylation at K32 (P = 8e-04);Loss of methylation at K32 (P = 8e-04);Loss of methylation at K32 (P = 8e-04);Loss of methylation at K32 (P = 8e-04);

MVP

0.43

ClinPred

0.42

GERP RS

4.9

Varity_R

0.27

gMVP

0.55

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