Genetic Variant NM_014735.5:c.1420C>A (chrX-47054605-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_014735.5(JADE3):c.1420C>A(p.His474Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,194,087 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 65 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000089 ( 0 hom., 4 hem., cov: 22)

Exomes 𝑓: 0.00020 ( 0 hom. 61 hem. )

Consequence

JADE3
NM_014735.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.48

Publications

0 publications found

Variant links:

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]

JADE3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.849

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.1420C>A	p.His474Asn	missense	Exon 9 of 11	NP_055550.1	Q92613
	JADE3	NM_001077445.3		c.1420C>A	p.His474Asn	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>A	p.His474Asn	missense	Exon 9 of 11	ENSP00000481850.1	Q92613
	JADE3	ENST00000611250.4	TSL:2	c.1420C>A	p.His474Asn	missense	Exon 9 of 11	ENSP00000479377.1	Q92613

Frequencies

GnomAD3 genomes

AF:

0.0000890

AC:

AN:

112373

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000323

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:

0.000169

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000113

AC:

AN:

167437

AF XY:

0.000107

show subpopulations

Gnomad AFR exome

AF:

0.0000852

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000238

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000201

AC:

217

AN:

1081714

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

349422

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26137

American (AMR)

AF:

0.00

AC:

AN:

34745

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19034

East Asian (EAS)

AF:

0.00

AC:

AN:

30091

South Asian (SAS)

AF:

0.00

AC:

AN:

52650

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36919

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4025

European-Non Finnish (NFE)

AF:

0.000256

AC:

213

AN:

832490

Other (OTH)

AF:

0.0000877

AC:

AN:

45623

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000890

AC:

AN:

112373

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

34533

show subpopulations

African (AFR)

AF:

0.0000323

AC:

AN:

30976

American (AMR)

AF:

0.00

AC:

AN:

10606

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2654

East Asian (EAS)

AF:

0.00

AC:

AN:

3580

South Asian (SAS)

AF:

0.00

AC:

AN:

2716

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6151

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.000169

AC:

AN:

53264

Other (OTH)

AF:

0.00

AC:

AN:

1502

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000110

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000825

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Benign

-0.042

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

M_CAP

Pathogenic

0.36

MetaRNN

Pathogenic

0.85

MetaSVM

Uncertain

-0.19

MutationAssessor

Pathogenic

3.0

PhyloP100

7.5

PrimateAI

Pathogenic

0.82

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.83

MVP

0.92

ClinPred

0.60

GERP RS

5.1

Varity_R

0.82

gMVP

0.75

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over