chrX-47054569-G-A

Variant names:

• chrX-47054569-G-A
• NM_014735.5:c.1384G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014735.5(JADE3):​c.1384G>A​(p.Glu462Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: JADE3 NM_014735.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.55

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32885632).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JADE3	NM_014735.5	c.1384G>A	p.Glu462Lys	missense_variant	Exon 9 of 11	ENST00000614628.5	NP_055550.1
JADE3	NM_001077445.3	c.1384G>A	p.Glu462Lys	missense_variant	Exon 9 of 11		NP_001070913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JADE3	ENST00000614628.5	c.1384G>A	p.Glu462Lys	missense_variant	Exon 9 of 11	1	NM_014735.5	ENSP00000481850.1
JADE3	ENST00000611250.4	c.1384G>A	p.Glu462Lys	missense_variant	Exon 9 of 11	2		ENSP00000479377.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 10, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1384G>A (p.E462K) alteration is located in exon 9 (coding exon 8) of the JADE3 gene. This alteration results from a G to A substitution at nucleotide position 1384, causing the glutamic acid (E) at amino acid position 462 to be replaced by a lysine (K). 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	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T;T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;.
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Uncertain	0.59	T
Sift4G	Uncertain	0.011	D;D
Polyphen		0.75	P;P
Vest4		0.36
MutPred		0.33		Gain of ubiquitination at E462 (P = 0.0039);Gain of ubiquitination at E462 (P = 0.0039);
MVP		0.80
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.66
gMVP		0.69

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-46913971;