Variant chrX-47058428-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM1BP4_StrongBS2

The NM_014735.5(JADE3):c.1823G>A(p.Ser608Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000422 in 1,209,567 control chromosomes in the GnomAD database, including 1 homozygotes. There are 16 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00015 ( 1 hom., 5 hem., cov: 22)

Exomes 𝑓: 0.000031 ( 0 hom. 11 hem. )

Consequence

JADE3
NM_014735.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.94

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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity JADE3_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.039627343).

BS2

High Hemizygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JADE3	NM_014735.5 linkuse as main transcript	c.1823G>A	p.Ser608Asn	missense_variant	11/11	ENST00000614628.5	NP_055550.1	Q92613A0A024R1A2
JADE3	NM_001077445.3 linkuse as main transcript	c.1823G>A	p.Ser608Asn	missense_variant	11/11		NP_001070913.1	Q92613A0A024R1A2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JADE3	ENST00000614628.5 linkuse as main transcript	c.1823G>A	p.Ser608Asn	missense_variant	11/11	1	NM_014735.5	ENSP00000481850.1		Q92613
JADE3	ENST00000611250.4 linkuse as main transcript	c.1823G>A	p.Ser608Asn	missense_variant	11/11	2		ENSP00000479377.1		Q92613

Frequencies

GnomAD3 genomes

AF:

0.000153

AC:

AN:

111404

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

AN XY:

33562

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

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:

0.00

Gnomad OTH

AF:

0.00133

GnomAD3 exomes

AF:

0.0000875

AC:

AN:

182872

Hom.:

AF XY:

0.0000741

AC XY:

AN XY:

67494

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000547

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.0000310

AC:

AN:

1098163

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

363519

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000881

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:

0.00

Gnomad4 OTH exome

AF:

0.0000651

GnomAD4 genome

AF:

0.000153

AC:

AN:

111404

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

AN XY:

33562

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00133

Bravo

AF:

0.000147

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 28, 2024

The c.1823G>A (p.S608N) alteration is located in exon 11 (coding exon 10) of the JADE3 gene. This alteration results from a G to A substitution at nucleotide position 1823, causing the serine (S) at amino acid position 608 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

T;T

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.61

T;.

M_CAP

Benign

0.045

MetaRNN

Benign

0.040

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;L

PrimateAI

Benign

0.30

Sift4G

Benign

0.26

T;T

Polyphen

0.0040

B;B

Vest4

0.10

MutPred

0.12

Loss of phosphorylation at S608 (P = 0.0211);Loss of phosphorylation at S608 (P = 0.0211);

MVP

0.42

ClinPred

0.065

GERP RS

3.6

Varity_R

0.22

gMVP

0.40

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over