X-46998256-C-T

Variant summary

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

The NM_014735.5(JADE3):c.263C>T(p.Thr88Ile) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: JADE3 NM_014735.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.345

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=0.18295327).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JADE3	NM_014735.5	c.263C>T	p.Thr88Ile	missense_variant	4/11	ENST00000614628.5
JADE3	NM_001077445.3	c.263C>T	p.Thr88Ile	missense_variant	4/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JADE3	ENST00000614628.5	c.263C>T	p.Thr88Ile	missense_variant	4/11	1	NM_014735.5	P1
JADE3	ENST00000611250.4	c.263C>T	p.Thr88Ile	missense_variant	4/11	2		P1
JADE3	ENST00000424392.5	c.263C>T	p.Thr88Ile	missense_variant	4/6	3
JADE3	ENST00000455411.1	c.263C>T	p.Thr88Ile	missense_variant	4/5	4

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1096072 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 361482

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 21

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

May 18, 2023

The c.263C>T (p.T88I) alteration is located in exon 4 (coding exon 3) of the JADE3 gene. This alteration results from a C to T substitution at nucleotide position 263, causing the threonine (T) at amino acid position 88 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	0.12
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
Cadd	Benign	14
Dann	Uncertain	1.0
FATHMM_MKL	Benign	0.11	N
LIST_S2	Uncertain	0.94	D;D;.;D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-0.82	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.2	D;.;.;D
REVEL	Benign	0.091
Sift	Uncertain	0.0050	D;.;.;D
Sift4G	Uncertain	0.025	D;D;D;D
Polyphen		0.29	.;B;B;.
Vest4		0.26, 0.20
MutPred		0.50		Loss of phosphorylation at T88 (P = 0.0298);Loss of phosphorylation at T88 (P = 0.0298);Loss of phosphorylation at T88 (P = 0.0298);Loss of phosphorylation at T88 (P = 0.0298);
MVP		0.31
ClinPred		0.92	D
GERP RS		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.17
gMVP		0.63

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-46857658;