rs138719055

Variant names:

• chrX-47054576-G-A
• rs138719055
• NM_014735.5:c.1391G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_014735.5(JADE3):​c.1391G>A​(p.Ser464Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000447 in 1,208,297 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S464G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00025 (0 hom., 4 hem., cov: 22)
  • Exomes 𝑓: 0.000024 (0 hom. 4 hem.)
• Consequence: JADE3 NM_014735.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.76
• Publications: 0 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.019809902).
• BS2: High Hemizygotes in GnomAd4 at 4 gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JADE3	NM_014735.5	MANE Select	c.1391G>A	p.Ser464Asn	missense	Exon 9 of 11	NP_055550.1	Q92613
	JADE3	NM_001077445.3		c.1391G>A	p.Ser464Asn	missense	Exon 9 of 11	NP_001070913.1	Q92613

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JADE3	ENST00000614628.5	TSL:1 MANE Select	c.1391G>A	p.Ser464Asn	missense	Exon 9 of 11	ENSP00000481850.1	Q92613
	JADE3	ENST00000611250.4	TSL:2	c.1391G>A	p.Ser464Asn	missense	Exon 9 of 11	ENSP00000479377.1	Q92613

Frequencies

GnomAD3 genomes AF: 0.000249 AC: 28 AN: 112506 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.000870

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000942

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000726 AC: 13 AN: 179057 AF XY: 0.0000620

Gnomad AFR exome AF: 0.000865

Gnomad AMR exome AF: 0.0000736

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000237 AC: 26 AN: 1095736 Hom.: 0 Cov.: 30 AF XY: 0.0000111 AC XY: 4 AN XY: 361348

African (AFR) AF: 0.000684 AC: 18 AN: 26335

American (AMR) AF: 0.0000570 AC: 2 AN: 35114

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19351

East Asian (EAS) AF: 0.00 AC: 0 AN: 30188

South Asian (SAS) AF: 0.00 AC: 0 AN: 53937

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39747

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4115

European-Non Finnish (NFE) AF: 0.00000357 AC: 3 AN: 840942

Other (OTH) AF: 0.0000652 AC: 3 AN: 46007

GnomAD4 genome AF: 0.000249 AC: 28 AN: 112561 Hom.: 0 Cov.: 22 AF XY: 0.000115 AC XY: 4 AN XY: 34711

African (AFR) AF: 0.000869 AC: 27 AN: 31087

American (AMR) AF: 0.0000941 AC: 1 AN: 10629

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2653

East Asian (EAS) AF: 0.00 AC: 0 AN: 3591

South Asian (SAS) AF: 0.00 AC: 0 AN: 2703

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6180

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53292

Other (OTH) AF: 0.00 AC: 0 AN: 1520

Alfa AF: 0.000285 Hom.: 1

Bravo AF: 0.000264

ESP6500AA AF: 0.00104 AC: 4

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000741 AC: 9

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	8.6
DANN	Benign	0.94
DEOGEN2	Benign	0.13	T
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.020	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		2.8
PrimateAI	Uncertain	0.50	T
Sift4G	Benign	0.10	T
Polyphen		0.13	B
Vest4		0.20
MVP		0.59
ClinPred		0.012	T
GERP RS		3.2
Varity_R		0.38
gMVP		0.62
Mutation Taster		=96/4	polymorphism

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: rs138719055; hg19: chrX-46913978;