NM_199320.4:c.2354C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_199320.4(JADE1):c.2354C>T(p.Pro785Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0011 in 1,614,128 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00078 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 1 hom. )

Consequence

JADE1
NM_199320.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.28

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

Bardet-Biedl syndrome
Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox
retinitis pigmentosa
Inheritance: AR Classification: LIMITED Submitted by: G2P
Senior-Loken syndrome
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

SCLT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013049036).

BS2

High AC in GnomAd4 at 119 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199320.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
JADE1	NM_199320.4	MANE Select	c.2354C>T	p.Pro785Leu	missense	Exon 11 of 11	NP_955352.1	Q6IE81-1
JADE1	NM_001287439.2		c.2354C>T	p.Pro785Leu	missense	Exon 11 of 11	NP_001274368.1	Q6IE81-1
JADE1	NM_001287440.2		c.2354C>T	p.Pro785Leu	missense	Exon 11 of 11	NP_001274369.1	Q6IE81-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
JADE1	ENST00000226319.11	TSL:5 MANE Select	c.2354C>T	p.Pro785Leu	missense	Exon 11 of 11	ENSP00000226319.6	Q6IE81-1
JADE1	ENST00000947587.1		c.2453C>T	p.Pro818Leu	missense	Exon 11 of 11	ENSP00000617646.1
JADE1	ENST00000887597.1		c.2426C>T	p.Pro809Leu	missense	Exon 12 of 12	ENSP00000557656.1

Frequencies

GnomAD3 genomes

AF:

0.000795

AC:

121

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00144

Gnomad OTH

AF:

0.000959

GnomAD2 exomes

AF:

0.000817

AC:

205

AN:

250898

AF XY:

0.000797

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00145

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.00113

AC:

1652

AN:

1461814

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

796

AN XY:

727206

show subpopulations

African (AFR)

AF:

0.000119

AC:

AN:

33478

American (AMR)

AF:

0.000425

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000230

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39672

South Asian (SAS)

AF:

0.000730

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.000131

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00137

AC:

1519

AN:

1111974

Other (OTH)

AF:

0.000563

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

195

292

390

487

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000781

AC:

119

AN:

152314

Hom.:

Cov.:

AF XY:

0.000685

AC XY:

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.0000962

AC:

AN:

41570

American (AMR)

AF:

0.000719

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000621

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00144

AC:

AN:

68022

Other (OTH)

AF:

0.000949

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00114

Hom.:

Bravo

AF:

0.000725

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000931

AC:

113

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00136

EpiControl

AF:

0.00130

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.057

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.051

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.012

MetaRNN

Benign

0.013

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

PhyloP100

4.3

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.3

REVEL

Benign

0.023

Sift

Uncertain

0.0060

Sift4G

Benign

0.32

Polyphen

0.039

Vest4

0.060

MVP

0.20

MPC

0.71

ClinPred

0.020

GERP RS

4.7

Varity_R

0.12

gMVP

0.26

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over