Variant X-47024740-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014735.5(JADE3):c.301G>T(p.Val101Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,070,309 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000019 ( 0 hom. 0 hem. )

Consequence

JADE3
NM_014735.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.68

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13055083).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JADE3	NM_014735.5 linkuse as main transcript	c.301G>T	p.Val101Leu	missense_variant	5/11	ENST00000614628.5	NP_055550.1	Q92613A0A024R1A2
JADE3	NM_001077445.3 linkuse as main transcript	c.301G>T	p.Val101Leu	missense_variant	5/11		NP_001070913.1	Q92613A0A024R1A2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
JADE3	ENST00000614628.5 linkuse as main transcript	c.301G>T	p.Val101Leu	missense_variant	5/11	1	NM_014735.5	ENSP00000481850.1	Q92613
JADE3	ENST00000611250.4 linkuse as main transcript	c.301G>T	p.Val101Leu	missense_variant	5/11	2		ENSP00000479377.1	Q92613
JADE3	ENST00000424392.5 linkuse as main transcript	c.301G>T	p.Val101Leu	missense_variant	5/6	3		ENSP00000391009.1	F2Z3N8
JADE3	ENST00000455411.1 linkuse as main transcript	c.301G>T	p.Val101Leu	missense_variant	5/5	4		ENSP00000400584.1	F2Z2B6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000593

AC:

AN:

168646

Hom.:

AF XY:

0.00

AC XY:

AN XY:

54788

show subpopulations

Gnomad AFR exome

AF:

0.0000792

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000187

AC:

AN:

1070309

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

338929

show subpopulations

Gnomad4 AFR exome

AF:

0.0000388

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:

0.00

Gnomad4 OTH exome

AF:

0.0000221

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

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

Jan 04, 2024

The c.301G>T (p.V101L) alteration is located in exon 5 (coding exon 4) of the JADE3 gene. This alteration results from a G to T substitution at nucleotide position 301, causing the valine (V) at amino acid position 101 to be replaced by a leucine (L). 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

0.11

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.71

CADD

Benign

5.7

DANN

Benign

0.86

DEOGEN2

Benign

0.057

.;T;T;T

FATHMM_MKL

Benign

0.50

LIST_S2

Uncertain

0.92

D;D;.;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

.;M;M;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.68

N;.;.;N

REVEL

Benign

0.048

Sift

Benign

0.32

T;.;.;T

Sift4G

Benign

0.33

T;T;T;T

Polyphen

0.0030

.;B;B;.

Vest4

0.17, 0.16

MutPred

0.47

Loss of methylation at K102 (P = 0.0386);Loss of methylation at K102 (P = 0.0386);Loss of methylation at K102 (P = 0.0386);Loss of methylation at K102 (P = 0.0386);

MVP

0.25

ClinPred

0.026

GERP RS

3.1

Varity_R

0.089

gMVP

0.56

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