4-128871517-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_199320.4(JADE1):c.1784A>G(p.His595Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

JADE1
NM_199320.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.67

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:

SCLT1 (HGNC:26406): (sodium channel and clathrin linker 1) This gene encodes an adaptor protein. Studies of a related gene in rat suggest that the encoded protein functions to link clathrin to the sodium channel protein type 10 subunit alpha protein. The encoded protein has also been identified as a component of distal appendages of centrioles that is necessary for ciliogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

SCLT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, JADE1

BP4

Computational evidence support a benign effect (MetaRNN=0.116698235).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JADE1	NM_199320.4 linkuse as main transcript	c.1784A>G	p.His595Arg	missense_variant	11/11	ENST00000226319.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JADE1	ENST00000226319.11 linkuse as main transcript	c.1784A>G	p.His595Arg	missense_variant	11/11	5	NM_199320.4	P1	Q6IE81-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251216

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135760

show subpopulations

Gnomad AFR exome

AF:

0.0000615

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

AF:

6.84e-7

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000264

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

Aug 09, 2021

The c.1784A>G (p.H595R) alteration is located in exon 11 (coding exon 10) of the JADE1 gene. This alteration results from a A to G substitution at nucleotide position 1784, causing the histidine (H) at amino acid position 595 to be replaced by an arginine (R). 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

0.059

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.41

Cadd

Benign

Dann

Benign

0.95

DEOGEN2

Benign

0.082

T;.;T;T;T

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.27

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.80

T;T;.;.;.

M_CAP

Benign

0.013

MetaRNN

Benign

0.12

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;.;N;N;N

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.55

N;N;N;.;.

REVEL

Benign

0.044

Sift

Benign

0.19

T;T;T;.;.

Sift4G

Benign

0.55

T;T;T;T;T

Polyphen

0.012

B;B;B;B;B

Vest4

0.24

MutPred

0.20

Gain of MoRF binding (P = 0.0252);.;Gain of MoRF binding (P = 0.0252);Gain of MoRF binding (P = 0.0252);Gain of MoRF binding (P = 0.0252);

MVP

0.49

MPC

0.86

ClinPred

0.084

GERP RS

1.8

Varity_R

0.042

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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