Variant chrX-47054616-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014735.5(JADE3):c.1431G>T(p.Gln477His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 112,389 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Consequence

JADE3
NM_014735.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.39

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JADE3	NM_014735.5 linkuse as main transcript	c.1431G>T	p.Gln477His	missense_variant	9/11	ENST00000614628.5	NP_055550.1	Q92613A0A024R1A2
JADE3	NM_001077445.3 linkuse as main transcript	c.1431G>T	p.Gln477His	missense_variant	9/11		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.1431G>T	p.Gln477His	missense_variant	9/11	1	NM_014735.5	ENSP00000481850.1		Q92613
JADE3	ENST00000611250.4 linkuse as main transcript	c.1431G>T	p.Gln477His	missense_variant	9/11	2		ENSP00000479377.1		Q92613

Frequencies

GnomAD3 genomes

AF:

0.00000890

AC:

AN:

112389

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34533

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000628

AC:

AN:

159334

Hom.:

AF XY:

0.00

AC XY:

AN XY:

50568

show subpopulations

Gnomad AFR exome

AF:

0.0000890

Gnomad AMR exome

AF:

0.00

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:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000890

AC:

AN:

112389

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34533

show subpopulations

Gnomad4 AFR

AF:

0.0000323

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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 22, 2024

The c.1431G>T (p.Q477H) alteration is located in exon 9 (coding exon 8) of the JADE3 gene. This alteration results from a G to T substitution at nucleotide position 1431, causing the glutamine (Q) at amino acid position 477 to be replaced by a histidine (H). 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

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.10

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.49

T;T

FATHMM_MKL

Uncertain

0.91

LIST_S2

Pathogenic

1.0

D;.

M_CAP

Uncertain

0.22

MetaRNN

Uncertain

0.65

D;D

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.7

M;M

PrimateAI

Uncertain

0.77

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.63

MutPred

0.32

Loss of stability (P = 0.0854);Loss of stability (P = 0.0854);

MVP

0.96

ClinPred

0.69

GERP RS

1.0

Varity_R

0.66

gMVP

0.81

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