chr4-128872081-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_199320.4(JADE1):​c.2348G>A​(p.Arg783Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000089 ( 0 hom. )

Consequence

JADE1
NM_199320.4 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.43
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.09757972).
BS2
High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
JADE1NM_199320.4 linkuse as main transcriptc.2348G>A p.Arg783Gln missense_variant 11/11 ENST00000226319.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
JADE1ENST00000226319.11 linkuse as main transcriptc.2348G>A p.Arg783Gln missense_variant 11/115 NM_199320.4 P1Q6IE81-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
250844
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135568
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:
0.0000441
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000889
AC:
13
AN:
1461798
Hom.:
0
Cov.:
32
AF XY:
0.00000963
AC XY:
7
AN XY:
727196
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:
0.0000108
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000370
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.0000330
AC:
4

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 GeneticsSep 17, 2021The c.2348G>A (p.R783Q) alteration is located in exon 11 (coding exon 10) of the JADE1 gene. This alteration results from a G to A substitution at nucleotide position 2348, causing the arginine (R) at amino acid position 783 to be replaced by a glutamine (Q). 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
0.073
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
23
DANN
Uncertain
0.98
DEOGEN2
Benign
0.051
T;.;T;T;T
Eigen
Benign
-0.26
Eigen_PC
Benign
-0.095
FATHMM_MKL
Uncertain
0.76
D
LIST_S2
Uncertain
0.90
D;D;.;.;.
M_CAP
Benign
0.0080
T
MetaRNN
Benign
0.098
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.26
N;.;N;N;N
MutationTaster
Benign
0.54
D;D;D
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-0.63
N;N;N;.;.
REVEL
Benign
0.047
Sift
Benign
0.38
T;T;T;.;.
Sift4G
Benign
0.33
T;T;T;T;T
Polyphen
0.010
B;B;B;B;B
Vest4
0.23
MVP
0.44
MPC
0.81
ClinPred
0.26
T
GERP RS
4.7
Varity_R
0.078
gMVP
0.17

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: rs778587937; hg19: chr4-129793236; API