4-128849025-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PM1 PM2 PP2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.412

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 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
• PP2: Missense variant where missense usually causes diseases, JADE1
• 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	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	c.342G>C	p.Lys114Asn	missense_variant	5/11	5	NM_199320.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

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	T
BayesDel_noAF	Benign	-0.44
Cadd	Benign	21
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	D
LIST_S2	Uncertain	0.94	D;.;D;D;.;D;.;D;D;D;.;D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.32	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.5	M;M;.;.;M;.;M;.;M;.;M;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.77	T
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	D
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.

Other links and lift over

hg19: chr4-129770180;