rs597320

Positions:

• chr11-134149466-G-A
• chr11-134149466-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032801.5(JAM3):​c.*285G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 569,238 control chromosomes in the GnomAD database, including 49,261 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (17530 hom., cov: 33)
  • Exomes 𝑓: 0.38 (31731 hom.)
• Consequence: JAM3 NM_032801.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.827

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 11-134149466-G-A is Benign according to our data. Variant chr11-134149466-G-A is described in ClinVar as [Benign]. Clinvar id is 1245738.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JAM3	NM_032801.5	c.*285G>A		3_prime_UTR_variant	9/9	ENST00000299106.9	NP_116190.3
JAM3	NM_001205329.2	c.*285G>A		3_prime_UTR_variant	8/8		NP_001192258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JAM3	ENST00000299106.9	c.*285G>A		3_prime_UTR_variant	9/9	1	NM_032801.5	ENSP00000299106.4
JAM3	ENST00000441717.3	c.*285G>A		3_prime_UTR_variant	8/8	2		ENSP00000395742.3

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70202 AN: 151964 Hom.: 17498 Cov.: 33

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.419

GnomAD4 exome AF: 0.382 AC: 159331 AN: 417158 Hom.: 31731 Cov.: 2 AF XY: 0.373 AC XY: 83455 AN XY: 223748

Gnomad4 AFR exome AF: 0.666

Gnomad4 AMR exome AF: 0.477

Gnomad4 ASJ exome AF: 0.315

Gnomad4 EAS exome AF: 0.472

Gnomad4 SAS exome AF: 0.307

Gnomad4 FIN exome AF: 0.425

Gnomad4 NFE exome AF: 0.364

Gnomad4 OTH exome AF: 0.383

GnomAD4 genome AF: 0.462 AC: 70287 AN: 152080 Hom.: 17530 Cov.: 33 AF XY: 0.463 AC XY: 34382 AN XY: 74336

Gnomad4 AFR AF: 0.662

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.417

Alfa AF: 0.379 Hom.: 15054

Bravo AF: 0.477

Asia WGS AF: 0.382 AC: 1327 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.7
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs597320; hg19: chr11-134019361;