X-47058454-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014735.5(JADE3):c.1849A>G(p.Lys617Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict 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: 2.49

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.089217186).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JADE3	NM_014735.5	c.1849A>G	p.Lys617Glu	missense_variant	11/11	ENST00000614628.5
JADE3	NM_001077445.3	c.1849A>G	p.Lys617Glu	missense_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JADE3	ENST00000614628.5	c.1849A>G	p.Lys617Glu	missense_variant	11/11	1	NM_014735.5	P1
JADE3	ENST00000611250.4	c.1849A>G	p.Lys617Glu	missense_variant	11/11	2		P1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 17, 2023

The c.1849A>G (p.K617E) alteration is located in exon 11 (coding exon 10) of the JADE3 gene. This alteration results from a A to G substitution at nucleotide position 1849, causing the lysine (K) at amino acid position 617 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	0.073
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	14
Dann	Uncertain	0.99
DEOGEN2	Benign	0.11	T;T
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.61	T;.
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.089	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;L
MutationTaster	Benign	0.96	D;D
PrimateAI	Benign	0.36	T
Sift4G	Benign	0.70	T;T
Polyphen		0.0010	B;B
Vest4		0.10
MutPred		0.17		Loss of ubiquitination at K617 (P = 4e-04);Loss of ubiquitination at K617 (P = 4e-04);
MVP		0.26
ClinPred		0.22	T
GERP RS		4.2
Varity_R		0.19
gMVP		0.28

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-46917856;