rs782758123

Variant names:

• chrX-46984913-G-A
• rs782758123
• NM_014735.5:c.19G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_014735.5(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. 15/20 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 NM_014735.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.646
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.02161339).
• BS2: High Hemizygotes in GnomAdExome4 at 21 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014735.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JADE3	NM_014735.5	MANE Select	c.19G>A	p.Val7Ile	missense	Exon 2 of 11	NP_055550.1	Q92613
	JADE3	NM_001077445.3		c.19G>A	p.Val7Ile	missense	Exon 2 of 11	NP_001070913.1	Q92613

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JADE3	ENST00000614628.5	TSL:1 MANE Select	c.19G>A	p.Val7Ile	missense	Exon 2 of 11	ENSP00000481850.1	Q92613
	JADE3	ENST00000611250.4	TSL:2	c.19G>A	p.Val7Ile	missense	Exon 2 of 11	ENSP00000479377.1	Q92613
	JADE3	ENST00000424392.5	TSL:3	c.19G>A	p.Val7Ile	missense	Exon 2 of 6	ENSP00000391009.1	F2Z3N8

Frequencies

GnomAD3 genomes AF: 0.00000895 AC: 1 AN: 111678 Hom.: 0 Cov.: 23

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

GnomAD2 exomes AF: 0.0000546 AC: 10 AN: 183213 AF XY: 0.000103

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000338 AC: 37 AN: 1095762 Hom.: 0 Cov.: 28 AF XY: 0.0000581 AC XY: 21 AN XY: 361180

African (AFR) AF: 0.00 AC: 0 AN: 26346

American (AMR) AF: 0.00 AC: 0 AN: 35198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19367

East Asian (EAS) AF: 0.00 AC: 0 AN: 30188

South Asian (SAS) AF: 0.000647 AC: 35 AN: 54070

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40523

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4123

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 839940

Other (OTH) AF: 0.0000435 AC: 2 AN: 46007

GnomAD4 genome AF: 0.00000895 AC: 1 AN: 111678 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33874

African (AFR) AF: 0.00 AC: 0 AN: 30686

American (AMR) AF: 0.00 AC: 0 AN: 10461

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3571

South Asian (SAS) AF: 0.000374 AC: 1 AN: 2671

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6014

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53203

Other (OTH) AF: 0.00 AC: 0 AN: 1499

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000659 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.38
DANN	Benign	0.72
DEOGEN2	Benign	0.059	T
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.65
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.022
Sift	Benign	0.56	T
Sift4G	Benign	0.40	T
Polyphen		0.0	B
Vest4		0.036
MutPred		0.16		Gain of methylation at K2 (P = 0.103)
MVP		0.068
ClinPred		0.0073	T
GERP RS		-2.4
Varity_R		0.036
gMVP		0.11
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs782758123; hg19: chrX-46844314;