NM_014735.5:c.79T>C

Variant names:

• chrX-46985745-T-C
• rs1927847782
• NM_014735.5:c.79T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014735.5(JADE3):​c.79T>C​(p.Tyr27His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000892 in 112,048 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 22)
• Consequence: JADE3 NM_014735.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.05
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15097794).

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.79T>C	p.Tyr27His	missense	Exon 3 of 11	NP_055550.1	Q92613
	JADE3	NM_001077445.3		c.79T>C	p.Tyr27His	missense	Exon 3 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.79T>C	p.Tyr27His	missense	Exon 3 of 11	ENSP00000481850.1	Q92613
	JADE3	ENST00000611250.4	TSL:2	c.79T>C	p.Tyr27His	missense	Exon 3 of 11	ENSP00000479377.1	Q92613
	JADE3	ENST00000424392.5	TSL:3	c.79T>C	p.Tyr27His	missense	Exon 3 of 6	ENSP00000391009.1	F2Z3N8

Frequencies

GnomAD3 genomes AF: 0.00000892 AC: 1 AN: 112048 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 26

GnomAD4 genome AF: 0.00000892 AC: 1 AN: 112048 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 34204

African (AFR) AF: 0.00 AC: 0 AN: 30757

American (AMR) AF: 0.00 AC: 0 AN: 10573

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2654

East Asian (EAS) AF: 0.00 AC: 0 AN: 3617

South Asian (SAS) AF: 0.00 AC: 0 AN: 2656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53264

Other (OTH) AF: 0.00 AC: 0 AN: 1499

Alfa AF: 0.00 Hom.: 0

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	0.14
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.057	T
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		3.0
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.50	N
REVEL	Benign	0.18
Sift	Benign	0.36	T
Sift4G	Benign	0.54	T
Polyphen		1.0	D
Vest4		0.32
MutPred		0.17		Loss of phosphorylation at Y27 (P = 0.031)
MVP		0.61
ClinPred		0.59	D
GERP RS		4.7
Varity_R		0.10
gMVP		0.52
Mutation Taster		=92/8	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: rs1927847782; hg19: chrX-46845146; COSMIC: COSV108049493;