X-47058684-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_014735.5(JADE3):c.2079G>A(p.Val693=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0005 in 1,209,758 control chromosomes in the GnomAD database, including 1 homozygotes. There are 189 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00040 (0 hom., 17 hem., cov: 23)
  • Exomes 𝑓: 0.00051 (1 hom. 172 hem.)
• Consequence: JADE3 NM_014735.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.10

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 Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant X-47058684-G-A is Benign according to our data. Variant chrX-47058684-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2603029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.1 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 17 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JADE3	NM_014735.5	c.2079G>A	p.Val693=	synonymous_variant	11/11	ENST00000614628.5
JADE3	NM_001077445.3	c.2079G>A	p.Val693=	synonymous_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JADE3	ENST00000614628.5	c.2079G>A	p.Val693=	synonymous_variant	11/11	1	NM_014735.5	P1
JADE3	ENST00000611250.4	c.2079G>A	p.Val693=	synonymous_variant	11/11	2		P1

Frequencies

GnomAD3 genomes AF: 0.000402 AC: 45 AN: 111877 Hom.: 0 Cov.: 23 AF XY: 0.000500 AC XY: 17 AN XY: 34033

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000191

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000819

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000695

Gnomad OTH AF: 0.000664

GnomAD3 exomes AF: 0.000340 AC: 62 AN: 182433 Hom.: 0 AF XY: 0.000328 AC XY: 22 AN XY: 66973

Gnomad AFR exome AF: 0.0000761

Gnomad AMR exome AF: 0.000329

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00144

Gnomad NFE exome AF: 0.000344

Gnomad OTH exome AF: 0.000222

GnomAD4 exome AF: 0.000510 AC: 560 AN: 1097829 Hom.: 1 Cov.: 31 AF XY: 0.000474 AC XY: 172 AN XY: 363201

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000199

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00116

Gnomad4 NFE exome AF: 0.000581

Gnomad4 OTH exome AF: 0.000369

GnomAD4 genome AF: 0.000402 AC: 45 AN: 111929 Hom.: 0 Cov.: 23 AF XY: 0.000499 AC XY: 17 AN XY: 34095

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000191

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000819

Gnomad4 NFE AF: 0.000696

Gnomad4 OTH AF: 0.000656

Alfa AF: 0.000540 Hom.: 4

Bravo AF: 0.000374

EpiCase AF: 0.000327

EpiControl AF: 0.000536

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

JADE3: BP4, BP7, BS1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.0
Dann	Benign	0.48

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

LitVar

Other links and lift over

dbSNP: rs151109669; hg19: chrX-46918086;