rs6855813

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_199320.4(JADE1):c.1985A>G(p.Asn662Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00509 in 1,614,130 control chromosomes in the GnomAD database, including 225 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.022 ( 110 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 115 hom. )

Consequence

JADE1
NM_199320.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.86

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014033616).

BP6

Variant 4-128871718-A-G is Benign according to our data. Variant chr4-128871718-A-G is described in ClinVar as [Benign]. Clinvar id is 776019.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JADE1	NM_199320.4 link	c.1985A>G	p.Asn662Ser	missense_variant	Exon 11 of 11	ENST00000226319.11	NP_955352.1	Q6IE81-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JADE1	ENST00000226319.11 link	c.1985A>G	p.Asn662Ser	missense_variant	Exon 11 of 11	5	NM_199320.4	ENSP00000226319.6		Q6IE81-1

Frequencies

GnomAD3 genomes

AF:

0.0224

AC:

3403

AN:

152162

Hom.:

109

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0735

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.00848

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00110

Gnomad OTH

AF:

0.0206

GnomAD3 exomes

AF:

0.00677

AC:

1699

AN:

250942

Hom.:

AF XY:

0.00549

AC XY:

745

AN XY:

135610

show subpopulations

Gnomad AFR exome

AF:

0.0735

Gnomad AMR exome

AF:

0.00399

Gnomad ASJ exome

AF:

0.000398

Gnomad EAS exome

AF:

0.00142

Gnomad SAS exome

AF:

0.00666

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000962

Gnomad OTH exome

AF:

0.00392

GnomAD4 exome

AF:

0.00328

AC:

4793

AN:

1461850

Hom.:

115

Cov.:

AF XY:

0.00318

AC XY:

2312

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.0773

Gnomad4 AMR exome

AF:

0.00465

Gnomad4 ASJ exome

AF:

0.000268

Gnomad4 EAS exome

AF:

0.00176

Gnomad4 SAS exome

AF:

0.00666

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000789

Gnomad4 OTH exome

AF:

0.00694

GnomAD4 genome

AF:

0.0225

AC:

3421

AN:

152280

Hom.:

110

Cov.:

AF XY:

0.0221

AC XY:

1646

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0737

Gnomad4 AMR

AF:

0.0124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.00849

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00110

Gnomad4 OTH

AF:

0.0208

Alfa

AF:

0.00502

Hom.:

Bravo

AF:

0.0250

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.0747

AC:

329

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.00786

AC:

954

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.00164

EpiControl

AF:

0.00136

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 27, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.026

T;.;T;T;T

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.27

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.85

T;T;.;.;.

MetaRNN

Benign

0.0014

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

N;.;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.12

N;N;N;.;.

REVEL

Benign

0.072

Sift

Benign

0.85

T;T;T;.;.

Sift4G

Benign

0.81

T;T;T;T;T

Polyphen

0.0

B;B;B;B;B

Vest4

0.041

MVP

0.34

MPC

0.55

ClinPred

0.0049

GERP RS

2.3

Varity_R

0.020

gMVP

0.085

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