Variant chrX-47039049-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_014735.5(JADE3):c.956C>T(p.Thr319Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,148,168 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.000023 ( 0 hom. 5 hem. )

Consequence

JADE3
NM_014735.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.07

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 -4 ACMG points.

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JADE3	NM_014735.5 linkuse as main transcript	c.956C>T	p.Thr319Met	missense_variant	8/11	ENST00000614628.5	NP_055550.1
JADE3	NM_001077445.3 linkuse as main transcript	c.956C>T	p.Thr319Met	missense_variant	8/11		NP_001070913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JADE3	ENST00000614628.5 linkuse as main transcript	c.956C>T	p.Thr319Met	missense_variant	8/11	1	NM_014735.5	ENSP00000481850	P1
JADE3	ENST00000611250.4 linkuse as main transcript	c.956C>T	p.Thr319Met	missense_variant	8/11	2		ENSP00000479377	P1

Frequencies

GnomAD3 genomes

AF:

0.0000271

AC:

AN:

110808

Hom.:

Cov.:

AF XY:

0.0000606

AC XY:

AN XY:

33020

show subpopulations

Gnomad AFR

AF:

0.0000657

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:

0.0000189

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000573

AC:

AN:

174658

Hom.:

AF XY:

0.0000167

AC XY:

AN XY:

59702

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000388

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:

0.000102

Gnomad OTH exome

AF:

0.000233

GnomAD4 exome

AF:

0.0000231

AC:

AN:

1037360

Hom.:

Cov.:

AF XY:

0.0000160

AC XY:

AN XY:

311782

show subpopulations

Gnomad4 AFR exome

AF:

0.0000397

Gnomad4 AMR exome

AF:

0.0000291

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000194

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000241

Gnomad4 OTH exome

AF:

0.0000227

GnomAD4 genome

AF:

0.0000271

AC:

AN:

110808

Hom.:

Cov.:

AF XY:

0.0000606

AC XY:

AN XY:

33020

show subpopulations

Gnomad4 AFR

AF:

0.0000657

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000189

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000110

ExAC

AF:

0.0000247

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

Mar 01, 2024

The c.956C>T (p.T319M) alteration is located in exon 8 (coding exon 7) of the JADE3 gene. This alteration results from a C to T substitution at nucleotide position 956, causing the threonine (T) at amino acid position 319 to be replaced by a methionine (M). 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

0.075

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

T;T

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.94

D;.

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.45

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.65

Sift4G

Uncertain

0.013

D;D

Polyphen

0.95

P;P

Vest4

0.22

MutPred

0.47

Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);

MVP

0.55

ClinPred

0.45

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.32

gMVP

0.89

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