4-128871735-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_199320.4(JADE1):​c.2002C>T​(p.Leu668Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000756 in 1,614,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000079 ( 0 hom. )

Consequence

JADE1
NM_199320.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.73
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.03274536).
BS2
High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
JADE1NM_199320.4 linkuse as main transcriptc.2002C>T p.Leu668Phe missense_variant 11/11 ENST00000226319.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
JADE1ENST00000226319.11 linkuse as main transcriptc.2002C>T p.Leu668Phe missense_variant 11/115 NM_199320.4 P1Q6IE81-1

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152158
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000558
AC:
14
AN:
250904
Hom.:
0
AF XY:
0.0000516
AC XY:
7
AN XY:
135600
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:
0.000124
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000794
AC:
116
AN:
1461842
Hom.:
0
Cov.:
32
AF XY:
0.0000784
AC XY:
57
AN XY:
727214
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:
0.000102
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152158
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000529
ExAC
AF:
0.0000659
AC:
8
EpiCase
AF:
0.000218
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsApr 07, 2023The c.2002C>T (p.L668F) alteration is located in exon 11 (coding exon 10) of the JADE1 gene. This alteration results from a C to T substitution at nucleotide position 2002, causing the leucine (L) at amino acid position 668 to be replaced by a phenylalanine (F). 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
0.061
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
21
DANN
Benign
0.97
DEOGEN2
Benign
0.053
T;.;T;T;T
Eigen
Benign
-0.27
Eigen_PC
Benign
-0.089
FATHMM_MKL
Benign
0.51
D
LIST_S2
Benign
0.69
T;T;.;.;.
M_CAP
Benign
0.0064
T
MetaRNN
Benign
0.033
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.34
N;.;N;N;N
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-0.46
N;N;N;.;.
REVEL
Benign
0.038
Sift
Benign
0.36
T;T;T;.;.
Sift4G
Benign
0.41
T;T;T;T;T
Polyphen
0.0
B;B;B;B;B
Vest4
0.013
MutPred
0.22
Loss of glycosylation at K670 (P = 0.0972);.;Loss of glycosylation at K670 (P = 0.0972);Loss of glycosylation at K670 (P = 0.0972);Loss of glycosylation at K670 (P = 0.0972);
MVP
0.15
MPC
0.76
ClinPred
0.027
T
GERP RS
3.7
Varity_R
0.051
gMVP
0.050

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.

Other links and lift over

dbSNP: rs771225620; hg19: chr4-129792890; API