Variant X-47027967-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_014735.5(JADE3):c.551A>T(p.Asn184Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000414 in 1,207,304 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.0000027 ( 0 hom. 1 hem. )

Consequence

JADE3
NM_014735.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.90

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.2253659).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JADE3	NM_014735.5 linkuse as main transcript	c.551A>T	p.Asn184Ile	missense_variant	6/11	ENST00000614628.5	NP_055550.1	Q92613A0A024R1A2
JADE3	NM_001077445.3 linkuse as main transcript	c.551A>T	p.Asn184Ile	missense_variant	6/11		NP_001070913.1	Q92613A0A024R1A2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
JADE3	ENST00000614628.5 linkuse as main transcript	c.551A>T	p.Asn184Ile	missense_variant	6/11	1	NM_014735.5	ENSP00000481850.1	Q92613
JADE3	ENST00000611250.4 linkuse as main transcript	c.551A>T	p.Asn184Ile	missense_variant	6/11	2		ENSP00000479377.1	Q92613
JADE3	ENST00000424392.5 linkuse as main transcript	c.551A>T	p.Asn184Ile	missense_variant	6/6	3		ENSP00000391009.1	F2Z3N8

Frequencies

GnomAD3 genomes

AF:

0.0000180

AC:

AN:

111098

Hom.:

Cov.:

AF XY:

0.0000300

AC XY:

AN XY:

33278

show subpopulations

Gnomad AFR

AF:

0.0000656

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000218

AC:

AN:

183396

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

67852

show subpopulations

Gnomad AFR exome

AF:

0.000152

Gnomad AMR exome

AF:

0.0000729

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1096206

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

361586

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.0000568

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000180

AC:

AN:

111098

Hom.:

Cov.:

AF XY:

0.0000300

AC XY:

AN XY:

33278

show subpopulations

Gnomad4 AFR

AF:

0.0000656

Gnomad4 AMR

AF:

0.00

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:

0.0000113

ExAC

AF:

0.00000824

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

Oct 01, 2024

The c.551A>T (p.N184I) alteration is located in exon 6 (coding exon 5) of the JADE3 gene. This alteration results from a A to T substitution at nucleotide position 551, causing the asparagine (N) at amino acid position 184 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

0.20

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.46

.;T;T

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.94

D;D;.

M_CAP

Benign

0.017

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.3

.;M;M

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-5.2

D;.;.

REVEL

Benign

0.17

Sift

Uncertain

0.019

D;.;.

Sift4G

Uncertain

0.032

D;D;D

Polyphen

0.53

.;P;P

Vest4

0.50, 0.51

MutPred

0.37

Loss of disorder (P = 0.0359);Loss of disorder (P = 0.0359);Loss of disorder (P = 0.0359);

MVP

0.48

ClinPred

0.36

GERP RS

4.6

Varity_R

0.76

gMVP

0.83

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