X-47058341-T-C

Variant names:

• chrX-47058341-T-C
• NM_014735.5:c.1736T>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014735.5(JADE3):​c.1736T>C​(p.Met579Thr) 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. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: JADE3 NM_014735.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.379

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.038554788).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JADE3	NM_014735.5	c.1736T>C	p.Met579Thr	missense_variant	Exon 11 of 11	ENST00000614628.5	NP_055550.1
JADE3	NM_001077445.3	c.1736T>C	p.Met579Thr	missense_variant	Exon 11 of 11		NP_001070913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JADE3	ENST00000614628.5	c.1736T>C	p.Met579Thr	missense_variant	Exon 11 of 11	1	NM_014735.5	ENSP00000481850.1
JADE3	ENST00000611250.4	c.1736T>C	p.Met579Thr	missense_variant	Exon 11 of 11	2		ENSP00000479377.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 12, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1736T>C (p.M579T) alteration is located in exon 11 (coding exon 10) of the JADE3 gene. This alteration results from a T to C substitution at nucleotide position 1736, causing the methionine (M) at amino acid position 579 to be replaced by a threonine (T). 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	0.063
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.38
DANN	Benign	0.60
DEOGEN2	Benign	0.066	T;T
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.37	T;.
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.039	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;M
PrimateAI	Benign	0.29	T
Sift4G	Benign	0.44	T;T
Polyphen		0.0	B;B
Vest4		0.034
MutPred		0.14		Gain of glycosylation at M579 (P = 0.0158);Gain of glycosylation at M579 (P = 0.0158);
MVP		0.043
ClinPred		0.059	T
GERP RS		-1.5
Varity_R		0.099
gMVP		0.21

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-46917743;