chrX-47024648-G-A

Variant names:

• chrX-47024648-G-A
• rs5952987
• NM_014735.5:c.285-76G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JADE3	NM_014735.5	MANE Select	c.285-76G>A		intron	N/A	NP_055550.1
	JADE3	NM_001077445.3		c.285-76G>A		intron	N/A	NP_001070913.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JADE3	ENST00000614628.5	TSL:1 MANE Select	c.285-76G>A		intron	N/A	ENSP00000481850.1
	JADE3	ENST00000611250.4	TSL:2	c.285-76G>A		intron	N/A	ENSP00000479377.1
	JADE3	ENST00000424392.5	TSL:3	c.285-76G>A		intron	N/A	ENSP00000391009.1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 22911 AN: 111612 Hom.: 2034 Cov.: 23

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

African (AFR) AF: 0.290 AC: 3733 AN: 12881

American (AMR) AF: 0.451 AC: 9077 AN: 20111

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 1659 AN: 11645

East Asian (EAS) AF: 0.383 AC: 9540 AN: 24901

South Asian (SAS) AF: 0.219 AC: 6185 AN: 28208

European-Finnish (FIN) AF: 0.143 AC: 5189 AN: 36395

Middle Eastern (MID) AF: 0.162 AC: 436 AN: 2692

European-Non Finnish (NFE) AF: 0.124 AC: 39556 AN: 319831

Other (OTH) AF: 0.178 AC: 4390 AN: 24714

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

African (AFR) AF: 0.295 AC: 9046 AN: 30716

American (AMR) AF: 0.333 AC: 3508 AN: 10541

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 361 AN: 2644

East Asian (EAS) AF: 0.366 AC: 1289 AN: 3519

South Asian (SAS) AF: 0.214 AC: 578 AN: 2698

European-Finnish (FIN) AF: 0.143 AC: 864 AN: 6047

Middle Eastern (MID) AF: 0.153 AC: 33 AN: 216

European-Non Finnish (NFE) AF: 0.128 AC: 6821 AN: 53094

Other (OTH) AF: 0.228 AC: 344 AN: 1512

Alfa AF: 0.172 Hom.: 15316

Bravo AF: 0.232

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.0
DANN	Benign	0.42
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism (auto)

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