4-128831772-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_199320.4(JADE1):c.14G>T(p.Arg5Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: JADE1 NM_199320.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.89

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, JADE1

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JADE1	NM_199320.4	c.14G>T	p.Arg5Leu	missense_variant	2/11	ENST00000226319.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JADE1	ENST00000226319.11	c.14G>T	p.Arg5Leu	missense_variant	2/11	5	NM_199320.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461842 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727224

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

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

Jun 17, 2022

The c.14G>T (p.R5L) alteration is located in exon 2 (coding exon 1) of the JADE1 gene. This alteration results from a G to T substitution at nucleotide position 14, causing the arginine (R) at amino acid position 5 to be replaced by a leucine (L). 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	0.67
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
Cadd	Uncertain	25
Dann	Uncertain	0.98
DEOGEN2	Benign	0.32	T;.;.;T;T;T;.;T;T;.;T;T;T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.95	D;.;D;D;.;D;.;.;D;D;D;.;D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.49	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.8	L;L;L;.;L;.;.;L;.;L;.;L;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Pathogenic	0.80	D
PROVEAN	Uncertain	-2.6	D;D;D;D;D;D;D;.;D;D;D;.;D
REVEL	Benign	0.16
Sift	Uncertain	0.0060	D;D;D;D;D;D;.;.;D;D;D;.;D
Sift4G	Uncertain	0.013	D;D;D;D;D;D;.;D;D;D;D;D;D
Polyphen		0.93	P;P;P;.;P;.;.;P;.;P;.;P;.
Vest4		0.55
MutPred		0.43		Gain of glycosylation at S8 (P = 0.0016);Gain of glycosylation at S8 (P = 0.0016);Gain of glycosylation at S8 (P = 0.0016);Gain of glycosylation at S8 (P = 0.0016);Gain of glycosylation at S8 (P = 0.0016);Gain of glycosylation at S8 (P = 0.0016);Gain of glycosylation at S8 (P = 0.0016);Gain of glycosylation at S8 (P = 0.0016);Gain of glycosylation at S8 (P = 0.0016);Gain of glycosylation at S8 (P = 0.0016);Gain of glycosylation at S8 (P = 0.0016);Gain of glycosylation at S8 (P = 0.0016);Gain of glycosylation at S8 (P = 0.0016);
MVP		0.36
MPC		1.4
ClinPred		0.94	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.39
gMVP		0.52

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: chr4-129752927;