NM_014735.5:c.1420C>T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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.

• 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

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 Uncertain_significance. Variant got 4 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JADE3	NM_014735.5	c.1420C>T	p.His474Tyr	missense_variant	Exon 9 of 11	ENST00000614628.5	NP_055550.1
JADE3	NM_001077445.3	c.1420C>T	p.His474Tyr	missense_variant	Exon 9 of 11		NP_001070913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JADE3	ENST00000614628.5	c.1420C>T	p.His474Tyr	missense_variant	Exon 9 of 11	1	NM_014735.5	ENSP00000481850.1
JADE3	ENST00000611250.4	c.1420C>T	p.His474Tyr	missense_variant	Exon 9 of 11	2		ENSP00000479377.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000240

Gnomad4 OTH exome AF: 0.0000219

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;.
M_CAP	Pathogenic	0.35	D
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Pathogenic	3.0	M;M
PrimateAI	Pathogenic	0.83	D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.85
MutPred		0.40		Loss of disorder (P = 0.0403);Loss of disorder (P = 0.0403);
MVP		0.98
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.80
gMVP		0.80

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-46914007;