X-47054567-A-T

Position:

• chrX-47054567-A-T

Variant summary

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

The NM_014735.5(JADE3):​c.1382A>T​(p.Lys461Ile) variant causes a missense change. 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: 5.76

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=0.3154142).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JADE3	NM_014735.5	c.1382A>T	p.Lys461Ile	missense_variant	9/11	ENST00000614628.5
JADE3	NM_001077445.3	c.1382A>T	p.Lys461Ile	missense_variant	9/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JADE3	ENST00000614628.5	c.1382A>T	p.Lys461Ile	missense_variant	9/11	1	NM_014735.5	P1
JADE3	ENST00000611250.4	c.1382A>T	p.Lys461Ile	missense_variant	9/11	2		P1

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2023

The c.1382A>T (p.K461I) alteration is located in exon 9 (coding exon 8) of the JADE3 gene. This alteration results from a A to T substitution at nucleotide position 1382, causing the lysine (K) at amino acid position 461 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	0.28
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T;T
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D;.
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.35	T
Sift4G	Uncertain	0.0030	D;D
Polyphen		0.58	P;P
Vest4		0.35
MutPred		0.37		Loss of ubiquitination at K461 (P = 0.0022);Loss of ubiquitination at K461 (P = 0.0022);
MVP		0.58
ClinPred		0.94	D
GERP RS		2.7
Varity_R		0.55
gMVP		0.58

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-46913969;