rs5952987

Positions:

• chrX-47024648-G-A
• chrX-47024648-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014735.5(JADE3):​c.285-76G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 593,045 control chromosomes in the GnomAD database, including 8,399 homozygotes. There are 29,507 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: 𝑓 0.21 (2036 hom., 6835 hem., cov: 23)
  • Exomes 𝑓: 0.17 (6363 hom. 22672 hem.)
• Consequence: JADE3 NM_014735.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.522

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JADE3	NM_014735.5	c.285-76G>A		intron_variant		ENST00000614628.5	NP_055550.1
JADE3	NM_001077445.3	c.285-76G>A		intron_variant			NP_001070913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JADE3	ENST00000614628.5	c.285-76G>A		intron_variant		1	NM_014735.5	ENSP00000481850.1
JADE3	ENST00000611250.4	c.285-76G>A		intron_variant		2		ENSP00000479377.1
JADE3	ENST00000424392.5	c.285-76G>A		intron_variant		3		ENSP00000391009.1
JADE3	ENST00000455411.1	c.285-76G>A		intron_variant		4		ENSP00000400584.1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 22911 AN: 111612 Hom.: 2034 Cov.: 23 AF XY: 0.202 AC XY: 6820 AN XY: 33810

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.223

GnomAD4 exome AF: 0.166 AC: 79765 AN: 481378 Hom.: 6363 AF XY: 0.174 AC XY: 22672 AN XY: 130402

Gnomad4 AFR exome AF: 0.290

Gnomad4 AMR exome AF: 0.451

Gnomad4 ASJ exome AF: 0.142

Gnomad4 EAS exome AF: 0.383

Gnomad4 SAS exome AF: 0.219

Gnomad4 FIN exome AF: 0.143

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.178

GnomAD4 genome AF: 0.205 AC: 22933 AN: 111667 Hom.: 2036 Cov.: 23 AF XY: 0.202 AC XY: 6835 AN XY: 33875

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.366

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.228

Alfa AF: 0.152 Hom.: 9537

Bravo AF: 0.232

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.0
DANN	Benign	0.42

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

LitVar

Other links and lift over

dbSNP: rs5952987; hg19: chrX-46884050; COSMIC: COSV54465146;