Genetic Variant NM_014735.5:c.310G>A (chrX-47024749-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014735.5(JADE3):c.310G>A(p.Val104Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,190,697 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 13 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000038 ( 0 hom. 12 hem. )

Consequence

JADE3
NM_014735.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.796

Publications

5 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0490492).

BS2

High Hemizygotes in GnomAdExome4 at 12 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.310G>A	p.Val104Ile	missense	Exon 5 of 11	NP_055550.1	Q92613
	JADE3	NM_001077445.3		c.310G>A	p.Val104Ile	missense	Exon 5 of 11	NP_001070913.1	Q92613

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
JADE3	ENST00000614628.5	TSL:1 MANE Select	c.310G>A	p.Val104Ile	missense	Exon 5 of 11	ENSP00000481850.1	Q92613
JADE3	ENST00000611250.4	TSL:2	c.310G>A	p.Val104Ile	missense	Exon 5 of 11	ENSP00000479377.1	Q92613
JADE3	ENST00000424392.5	TSL:3	c.310G>A	p.Val104Ile	missense	Exon 5 of 6	ENSP00000391009.1	F2Z3N8

Frequencies

GnomAD3 genomes

AF:

0.0000358

AC:

AN:

111766

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000950

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:

0.0000564

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000292

AC:

AN:

171482

AF XY:

0.0000350

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000642

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000380

AC:

AN:

1078931

Hom.:

Cov.:

AF XY:

0.0000346

AC XY:

AN XY:

346383

show subpopulations

African (AFR)

AF:

0.0000386

AC:

AN:

25900

American (AMR)

AF:

0.0000294

AC:

AN:

33980

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19066

East Asian (EAS)

AF:

0.00

AC:

AN:

29884

South Asian (SAS)

AF:

0.00

AC:

AN:

52029

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40407

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4083

European-Non Finnish (NFE)

AF:

0.0000471

AC:

AN:

828157

Other (OTH)

AF:

0.00

AC:

AN:

45425

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

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:

0.0000358

AC:

AN:

111766

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

33952

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30723

American (AMR)

AF:

0.0000950

AC:

AN:

10525

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2652

East Asian (EAS)

AF:

0.00

AC:

AN:

3551

South Asian (SAS)

AF:

0.00

AC:

AN:

2687

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6051

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.0000564

AC:

AN:

53156

Other (OTH)

AF:

0.00

AC:

AN:

1498

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000412

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

Benign

0.070

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.9

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.061

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.83

M_CAP

Benign

0.0072

MetaRNN

Benign

0.049

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.89

PhyloP100

0.80

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.38

REVEL

Benign

0.038

Sift

Benign

0.32

Sift4G

Benign

0.44

Polyphen

0.0040

Vest4

0.047

MVP

0.12

ClinPred

0.031

GERP RS

1.0

Varity_R

0.044

gMVP

0.40

Mutation Taster

=100/0

polymorphism

(source)

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

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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