X-47054605-C-T

Variant names:

• chrX-47054605-C-T
• rs200186609
• NM_014735.5:c.1420C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_014735.5(JADE3):​c.1420C>T​(p.His474Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000277 in 1,081,719 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H474N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000028 (0 hom. 0 hem.)
• Consequence: JADE3 NM_014735.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.48
• 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.875

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.1420C>T	p.His474Tyr	missense	Exon 9 of 11	NP_055550.1	Q92613
	JADE3	NM_001077445.3		c.1420C>T	p.His474Tyr	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.1420C>T	p.His474Tyr	missense	Exon 9 of 11	ENSP00000481850.1	Q92613
	JADE3	ENST00000611250.4	TSL:2	c.1420C>T	p.His474Tyr	missense	Exon 9 of 11	ENSP00000479377.1	Q92613

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000277 AC: 3 AN: 1081719 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 349425

African (AFR) AF: 0.00 AC: 0 AN: 26137

American (AMR) AF: 0.00 AC: 0 AN: 34746

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19034

East Asian (EAS) AF: 0.00 AC: 0 AN: 30091

South Asian (SAS) AF: 0.00 AC: 0 AN: 52650

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36918

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4025

European-Non Finnish (NFE) AF: 0.00000240 AC: 2 AN: 832495

Other (OTH) AF: 0.0000219 AC: 1 AN: 45623

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.41
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Pathogenic	0.35	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		7.5
PrimateAI	Pathogenic	0.83	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.85
MutPred		0.40		Loss of disorder (P = 0.0403)
MVP		0.98
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.80
gMVP		0.80
Mutation Taster		=79/21	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: rs200186609; hg19: chrX-46914007;