X-47054420-G-T

Variant names:

• chrX-47054420-G-T
• NM_014735.5:c.1235G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014735.5(JADE3):​c.1235G>T​(p.Arg412Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000273 in 1,097,734 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000027 (0 hom. 1 hem.)
• Consequence: JADE3 NM_014735.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.869

Genes affected

JADE3 (HGNC:22982): (jade family PHD finger 3) This gene encodes a member of a family of large proteins containing PHD (plant homeo domain)-type zinc fingers. The encoded protein may be associated in a nuclear complex that functions in histone H4 acetylation. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.119145215).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JADE3	NM_014735.5	c.1235G>T	p.Arg412Leu	missense_variant	Exon 9 of 11	ENST00000614628.5	NP_055550.1
JADE3	NM_001077445.3	c.1235G>T	p.Arg412Leu	missense_variant	Exon 9 of 11		NP_001070913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JADE3	ENST00000614628.5	c.1235G>T	p.Arg412Leu	missense_variant	Exon 9 of 11	1	NM_014735.5	ENSP00000481850.1
JADE3	ENST00000611250.4	c.1235G>T	p.Arg412Leu	missense_variant	Exon 9 of 11	2		ENSP00000479377.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000273 AC: 3 AN: 1097734 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 1 AN XY: 363098

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: 0.00000356

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.40	T;T
FATHMM_MKL	Benign	0.088	N
LIST_S2	Uncertain	0.94	D;.
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Benign	0.22	T
Sift4G	Benign	0.084	T;T
Polyphen		0.10	B;B
Vest4		0.30
MutPred		0.39		Loss of phosphorylation at S409 (P = 0.1065);Loss of phosphorylation at S409 (P = 0.1065);
MVP		0.28
ClinPred		0.090	T
GERP RS		-7.3
Varity_R		0.14
gMVP		0.63

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: chrX-46913822;