4-128843004-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_199320.4(JADE1):c.104C>T(p.Ser35Phe) 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: 3.37

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 1 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=0.22555056).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JADE1	NM_199320.4	c.104C>T	p.Ser35Phe	missense_variant	3/11	ENST00000226319.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JADE1	ENST00000226319.11	c.104C>T	p.Ser35Phe	missense_variant	3/11	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

Nov 02, 2023

The c.104C>T (p.S35F) alteration is located in exon 3 (coding exon 2) of the JADE1 gene. This alteration results from a C to T substitution at nucleotide position 104, causing the serine (S) at amino acid position 35 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	0.13
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.11	T;.;.;T;T;T;T;T;.;T;T;T
Eigen	Benign	0.19
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.91	D;.;D;D;.;D;.;D;D;D;.;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.23	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L;L;L;.;L;.;L;.;L;.;L;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.9	N;N;N;D;N;D;.;D;N;D;.;D
REVEL	Benign	0.096
Sift	Uncertain	0.0080	D;D;D;D;D;D;.;D;D;D;.;D
Sift4G	Uncertain	0.036	D;D;D;D;D;D;D;D;D;D;D;D
Polyphen		0.77	P;D;P;.;P;.;P;.;D;.;P;.
Vest4		0.55
MutPred		0.45		Gain of glycosylation at S34 (P = 0.0017);Gain of glycosylation at S34 (P = 0.0017);Gain of glycosylation at S34 (P = 0.0017);Gain of glycosylation at S34 (P = 0.0017);Gain of glycosylation at S34 (P = 0.0017);Gain of glycosylation at S34 (P = 0.0017);Gain of glycosylation at S34 (P = 0.0017);Gain of glycosylation at S34 (P = 0.0017);Gain of glycosylation at S34 (P = 0.0017);Gain of glycosylation at S34 (P = 0.0017);Gain of glycosylation at S34 (P = 0.0017);Gain of glycosylation at S34 (P = 0.0017);
MVP		0.26
MPC		1.3
ClinPred		0.83	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.35

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: chr4-129764159;