X-47054092-C-G

Variant names:

• chrX-47054092-C-G
• rs2239791
• NM_014735.5:c.973-66C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014735.5(JADE3):​c.973-66C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 756,387 control chromosomes in the GnomAD database, including 8,333 homozygotes. There are 33,924 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 0.16 (1276 hom., 5220 hem., cov: 22)
  • Exomes 𝑓: 0.16 (7057 hom. 28704 hem.)
• Consequence: JADE3 NM_014735.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223
• Publications: 5 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JADE3	NM_014735.5	c.973-66C>G		intron_variant	Intron 8 of 10	ENST00000614628.5	NP_055550.1
JADE3	NM_001077445.3	c.973-66C>G		intron_variant	Intron 8 of 10		NP_001070913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JADE3	ENST00000614628.5	c.973-66C>G		intron_variant	Intron 8 of 10	1	NM_014735.5	ENSP00000481850.1
JADE3	ENST00000611250.4	c.973-66C>G		intron_variant	Intron 8 of 10	2		ENSP00000479377.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 17859 AN: 110401 Hom.: 1273 Cov.: 22

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.122

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.198

GnomAD4 exome AF: 0.156 AC: 100844 AN: 645933 Hom.: 7057 AF XY: 0.167 AC XY: 28704 AN XY: 172345

African (AFR) AF: 0.141 AC: 2271 AN: 16064

American (AMR) AF: 0.443 AC: 8657 AN: 19532

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 1795 AN: 12618

East Asian (EAS) AF: 0.384 AC: 10211 AN: 26572

South Asian (SAS) AF: 0.226 AC: 7718 AN: 34085

European-Finnish (FIN) AF: 0.152 AC: 5382 AN: 35494

Middle Eastern (MID) AF: 0.156 AC: 311 AN: 1992

European-Non Finnish (NFE) AF: 0.127 AC: 59501 AN: 469364

Other (OTH) AF: 0.165 AC: 4998 AN: 30212

GnomAD4 genome AF: 0.162 AC: 17862 AN: 110454 Hom.: 1276 Cov.: 22 AF XY: 0.159 AC XY: 5220 AN XY: 32734

African (AFR) AF: 0.138 AC: 4200 AN: 30445

American (AMR) AF: 0.321 AC: 3279 AN: 10201

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 351 AN: 2632

East Asian (EAS) AF: 0.366 AC: 1270 AN: 3472

South Asian (SAS) AF: 0.215 AC: 561 AN: 2610

European-Finnish (FIN) AF: 0.149 AC: 865 AN: 5803

Middle Eastern (MID) AF: 0.129 AC: 28 AN: 217

European-Non Finnish (NFE) AF: 0.131 AC: 6914 AN: 52889

Other (OTH) AF: 0.203 AC: 306 AN: 1509

Alfa AF: 0.159 Hom.: 924

Bravo AF: 0.183

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.8
DANN	Benign	0.69
PhyloP100		-0.22
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: rs2239791; hg19: chrX-46913494;