X-46998256-C-G

Variant names:

• chrX-46998256-C-G
• rs782765097
• NM_014735.5:c.263C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014735.5(JADE3):​c.263C>G​(p.Thr88Ser) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T88I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 21)
• Consequence: JADE3 NM_014735.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.345
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.028608918).

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.263C>G	p.Thr88Ser	missense	Exon 4 of 11	NP_055550.1	Q92613
	JADE3	NM_001077445.3		c.263C>G	p.Thr88Ser	missense	Exon 4 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.263C>G	p.Thr88Ser	missense	Exon 4 of 11	ENSP00000481850.1	Q92613
	JADE3	ENST00000611250.4	TSL:2	c.263C>G	p.Thr88Ser	missense	Exon 4 of 11	ENSP00000479377.1	Q92613
	JADE3	ENST00000424392.5	TSL:3	c.263C>G	p.Thr88Ser	missense	Exon 4 of 6	ENSP00000391009.1	F2Z3N8

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 21

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.52
DANN	Benign	0.49
DEOGEN2	Benign	0.051	T
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.22	N
PhyloP100		0.34
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.024
Sift	Benign	0.47	T
Sift4G	Benign	0.81	T
Polyphen		0.0020	B
Vest4		0.065
MutPred		0.31		Gain of disorder (P = 0.0401)
MVP		0.40
ClinPred		0.065	T
GERP RS		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.082
gMVP		0.35
Mutation Taster		=96/4	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: rs782765097; hg19: chrX-46857658;