Variant 4-128849027-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_199320.4(JADE1):c.344A>G(p.Tyr115Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

JADE1
NM_199320.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.37

Variant links:

Genes affected

JADE1 (HGNC:30027): (jade family PHD finger 1) Enables transcription coactivator activity. Involved in histone acetylation and negative regulation of canonical Wnt signaling pathway. Acts upstream of or within negative regulation of G1/S transition of mitotic cell cycle. Located in several cellular components, including ciliary basal body; cytosol; and nuclear speck. Part of histone acetyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]

JADE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JADE1	NM_199320.4 linkuse as main transcript	c.344A>G	p.Tyr115Cys	missense_variant	5/11	ENST00000226319.11	NP_955352.1	Q6IE81-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JADE1	ENST00000226319.11 linkuse as main transcript	c.344A>G	p.Tyr115Cys	missense_variant	5/11	5	NM_199320.4	ENSP00000226319.6		Q6IE81-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251430

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135896

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461840

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000144

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

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

Dec 28, 2022

The c.344A>G (p.Y115C) alteration is located in exon 5 (coding exon 4) of the JADE1 gene. This alteration results from a A to G substitution at nucleotide position 344, causing the tyrosine (Y) at amino acid position 115 to be replaced by a cysteine (C). 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

0.15

BayesDel_addAF

Uncertain

0.035

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

T;.;.;T;T;T;T;T;.;T;T;T

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.84

LIST_S2

Pathogenic

0.98

D;.;D;D;.;D;.;D;D;D;.;D

M_CAP

Benign

0.064

MetaRNN

Uncertain

0.70

D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.50

MutationAssessor

Uncertain

2.6

M;M;.;.;M;.;M;.;M;.;M;.

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-4.6

D;D;D;D;D;D;.;D;D;D;.;D

REVEL

Uncertain

0.37

Sift

Uncertain

0.016

D;D;D;D;D;D;.;D;D;D;.;D

Sift4G

Uncertain

0.052

T;D;D;T;T;T;T;T;D;T;T;D

Polyphen

0.99

D;D;D;.;D;.;D;.;D;.;D;.

Vest4

0.73

MutPred

0.70

Gain of glycosylation at Y115 (P = 0.0194);Gain of glycosylation at Y115 (P = 0.0194);.;Gain of glycosylation at Y115 (P = 0.0194);Gain of glycosylation at Y115 (P = 0.0194);Gain of glycosylation at Y115 (P = 0.0194);Gain of glycosylation at Y115 (P = 0.0194);Gain of glycosylation at Y115 (P = 0.0194);Gain of glycosylation at Y115 (P = 0.0194);Gain of glycosylation at Y115 (P = 0.0194);Gain of glycosylation at Y115 (P = 0.0194);Gain of glycosylation at Y115 (P = 0.0194);

MVP

0.41

MPC

1.8

ClinPred

0.97

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.26

gMVP

0.91

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

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