X-47054575-A-G

Variant names:

• chrX-47054575-A-G
• rs1556372993
• NM_014735.5:c.1390A>G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_014735.5(JADE3):​c.1390A>G​(p.Ser464Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00001 in 1,096,080 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000010 (0 hom. 4 hem.)
• Consequence: JADE3 NM_014735.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.92

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.23148024).
• BS2: High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JADE3	NM_014735.5	c.1390A>G	p.Ser464Gly	missense_variant	Exon 9 of 11	ENST00000614628.5	NP_055550.1
JADE3	NM_001077445.3	c.1390A>G	p.Ser464Gly	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.1390A>G	p.Ser464Gly	missense_variant	Exon 9 of 11	1	NM_014735.5	ENSP00000481850.1
JADE3	ENST00000611250.4	c.1390A>G	p.Ser464Gly	missense_variant	Exon 9 of 11	2		ENSP00000479377.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.00000558 AC: 1 AN: 179338 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 64704

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000124

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000100 AC: 11 AN: 1096080 Hom.: 0 Cov.: 30 AF XY: 0.0000111 AC XY: 4 AN XY: 361660

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: 0.00000951

Gnomad4 OTH exome AF: 0.0000652

GnomAD4 genome Cov.: 23

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 25, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1390A>G (p.S464G) alteration is located in exon 9 (coding exon 8) of the JADE3 gene. This alteration results from a A to G substitution at nucleotide position 1390, causing the serine (S) at amino acid position 464 to be replaced by a glycine (G). 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	0.096
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;T
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.82	T;.
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Benign	0.44	T
Sift4G	Uncertain	0.045	D;D
Polyphen		0.75	P;P
Vest4		0.46
MutPred		0.17		Loss of phosphorylation at S464 (P = 0.0745);Loss of phosphorylation at S464 (P = 0.0745);
MVP		0.82
ClinPred		0.67	D
GERP RS		4.9
Varity_R		0.53
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1556372993; hg19: chrX-46913977;