4-128849016-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_199320.4(JADE1):c.333G>T(p.Arg111Ser) 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: 0.291

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 2 ACMG points.

• 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=0.3919493).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JADE1	NM_199320.4	c.333G>T	p.Arg111Ser	missense_variant	5/11	ENST00000226319.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JADE1	ENST00000226319.11	c.333G>T	p.Arg111Ser	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

Feb 05, 2024

The c.333G>T (p.R111S) alteration is located in exon 5 (coding exon 4) of the JADE1 gene. This alteration results from a G to T substitution at nucleotide position 333, causing the arginine (R) at amino acid position 111 to be replaced by a serine (S). 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	0.59
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
Cadd	Benign	19
Dann	Uncertain	0.99
DEOGEN2	Benign	0.25	T;.;.;T;T;T;T;T;.;T;T;T
Eigen	Benign	-0.047
Eigen_PC	Benign	0.092
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.96	D;.;D;D;.;D;.;D;D;D;.;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.39	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.5	N;N;D;N;N;N;.;N;N;N;.;N
REVEL	Benign	0.17
Sift	Benign	0.34	T;T;T;T;T;T;.;T;T;T;.;D
Sift4G	Benign	0.36	T;T;D;T;T;T;T;T;T;T;T;T
Polyphen		0.21	B;B;B;.;B;.;B;.;B;.;B;.
Vest4		0.71
MutPred		0.63		Gain of glycosylation at Y115 (P = 0.0194);Gain of glycosylation at Y115 (P = 0.0194);.;Gain of glycosylation at Y115 (P = 0.0194);Gain of glycosylation at Y115 (P = 0.0194);Gain of glycosylation at Y115 (P = 0.0194);Gain of glycosylation at Y115 (P = 0.0194);Gain of glycosylation at Y115 (P = 0.0194);Gain of glycosylation at Y115 (P = 0.0194);Gain of glycosylation at Y115 (P = 0.0194);Gain of glycosylation at Y115 (P = 0.0194);Gain of glycosylation at Y115 (P = 0.0194);
MVP		0.62
MPC		0.90
ClinPred		0.83	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.91

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-129770171;