Variant chr4-128849025-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4

The NM_199320.4(JADE1):c.342G>C(p.Lys114Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

JADE1
NM_199320.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.412

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM1

In a cross_link Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) (size 0) in uniprot entity JADE1_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31934845).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JADE1	NM_199320.4 linkuse as main transcript	c.342G>C	p.Lys114Asn	missense_variant	5/11	ENST00000226319.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JADE1	ENST00000226319.11 linkuse as main transcript	c.342G>C	p.Lys114Asn	missense_variant	5/11	5	NM_199320.4	P1	Q6IE81-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

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

Oct 13, 2021

The c.342G>C (p.K114N) alteration is located in exon 5 (coding exon 4) of the JADE1 gene. This alteration results from a G to C substitution at nucleotide position 342, causing the lysine (K) at amino acid position 114 to be replaced by an asparagine (N). 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

Pathogenic

0.79

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

T;.;.;T;T;T;T;T;.;T;T;T

Eigen

Benign

-0.026

Eigen_PC

Benign

-0.063

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.94

D;.;D;D;.;D;.;D;D;D;.;D

M_CAP

Benign

0.025

MetaRNN

Benign

0.32

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.5

M;M;.;.;M;.;M;.;M;.;M;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-3.3

D;D;D;D;D;D;.;D;D;D;.;D

REVEL

Benign

0.16

Sift

Benign

0.072

T;T;D;D;T;D;.;D;T;D;.;D

Sift4G

Uncertain

0.011

D;D;D;D;D;D;D;D;D;D;D;D

Polyphen

0.77

P;B;P;.;P;.;P;.;B;.;P;.

Vest4

0.42

MutPred

0.48

Loss of methylation at K114 (P = 0.0027);Loss of methylation at K114 (P = 0.0027);.;Loss of methylation at K114 (P = 0.0027);Loss of methylation at K114 (P = 0.0027);Loss of methylation at K114 (P = 0.0027);Loss of methylation at K114 (P = 0.0027);Loss of methylation at K114 (P = 0.0027);Loss of methylation at K114 (P = 0.0027);Loss of methylation at K114 (P = 0.0027);Loss of methylation at K114 (P = 0.0027);Loss of methylation at K114 (P = 0.0027);

MVP

0.51

MPC

0.86

ClinPred

0.97

GERP RS

0.13

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.37

gMVP

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over