Variant chr11-134139965-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032801.5(JAM3):c.142+49T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,406,516 control chromosomes in the GnomAD database, including 18,822 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2467 hom., cov: 32)

Exomes 𝑓: 0.16 ( 16355 hom. )

Consequence

JAM3
NM_032801.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.68

Variant links:

Genes affected

JAM3 (HGNC:15532): (junctional adhesion molecule 3) Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seals around cells and serving as a physical barrier to prevent solutes and water from passing freely through the paracellular space. The protein encoded by this immunoglobulin superfamily gene member is localized in the tight junctions between high endothelial cells. Unlike other proteins in this family, the this protein is unable to adhere to leukocyte cell lines and only forms weak homotypic interactions. The encoded protein is a member of the junctional adhesion molecule protein family and acts as a receptor for another member of this family. A mutation in an intron of this gene is associated with hemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Apr 2011]

JAM3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 11-134139965-T-C is Benign according to our data. Variant chr11-134139965-T-C is described in ClinVar as [Benign]. Clinvar id is 1288505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JAM3	NM_032801.5 linkuse as main transcript	c.142+49T>C		intron_variant		ENST00000299106.9	NP_116190.3
JAM3	NM_001205329.2 linkuse as main transcript	c.142+49T>C		intron_variant			NP_001192258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JAM3	ENST00000299106.9 linkuse as main transcript	c.142+49T>C		intron_variant		1	NM_032801.5	ENSP00000299106	P1	Q9BX67-1

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

26757

AN:

151928

Hom.:

2459

Cov.:

show subpopulations

Gnomad AFR

AF:

0.212

Gnomad AMI

AF:

0.145

Gnomad AMR

AF:

0.164

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.142

Gnomad SAS

AF:

0.0752

Gnomad FIN

AF:

0.243

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.152

GnomAD3 exomes

AF:

0.158

AC:

39222

AN:

248528

Hom.:

3300

AF XY:

0.153

AC XY:

20617

AN XY:

134572

show subpopulations

Gnomad AFR exome

AF:

0.213

Gnomad AMR exome

AF:

0.154

Gnomad ASJ exome

AF:

0.117

Gnomad EAS exome

AF:

0.145

Gnomad SAS exome

AF:

0.0850

Gnomad FIN exome

AF:

0.239

Gnomad NFE exome

AF:

0.163

Gnomad OTH exome

AF:

0.147

GnomAD4 exome

AF:

0.157

AC:

196437

AN:

1254470

Hom.:

16355

Cov.:

AF XY:

0.154

AC XY:

97642

AN XY:

635094

show subpopulations

Gnomad4 AFR exome

AF:

0.209

Gnomad4 AMR exome

AF:

0.157

Gnomad4 ASJ exome

AF:

0.118

Gnomad4 EAS exome

AF:

0.129

Gnomad4 SAS exome

AF:

0.0846

Gnomad4 FIN exome

AF:

0.232

Gnomad4 NFE exome

AF:

0.160

Gnomad4 OTH exome

AF:

0.147

GnomAD4 genome

AF:

0.176

AC:

26791

AN:

152046

Hom.:

2467

Cov.:

AF XY:

0.179

AC XY:

13289

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.212

Gnomad4 AMR

AF:

0.165

Gnomad4 ASJ

AF:

0.121

Gnomad4 EAS

AF:

0.142

Gnomad4 SAS

AF:

0.0763

Gnomad4 FIN

AF:

0.243

Gnomad4 NFE

AF:

0.161

Gnomad4 OTH

AF:

0.151

Alfa

AF:

0.155

Hom.:

4017

Bravo

AF:

0.173

Asia WGS

AF:

0.0980

AC:

340

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.1

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over