rs597320

Variant names:

• chr11-134149466-G-A
• rs597320
• NM_032801.5:c.*285G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 16 publications found

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 Gene-Disease associations (from GenCC):

• porencephaly-microcephaly-bilateral congenital cataract syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• 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 rank	MANE	Protein	UniProt
JAM3	NM_032801.5	c.*285G>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000299106.9	NP_116190.3
JAM3	NM_001205329.2	c.*285G>A		3_prime_UTR_variant	Exon 8 of 8		NP_001192258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JAM3	ENST00000299106.9	c.*285G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_032801.5	ENSP00000299106.4
JAM3	ENST00000441717.3	c.*285G>A		3_prime_UTR_variant	Exon 8 of 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

African (AFR) AF: 0.666 AC: 8073 AN: 12116

American (AMR) AF: 0.477 AC: 10697 AN: 22420

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 4123 AN: 13088

East Asian (EAS) AF: 0.472 AC: 12303 AN: 26040

South Asian (SAS) AF: 0.307 AC: 14849 AN: 48296

European-Finnish (FIN) AF: 0.425 AC: 9989 AN: 23506

Middle Eastern (MID) AF: 0.277 AC: 502 AN: 1810

European-Non Finnish (NFE) AF: 0.364 AC: 89803 AN: 246414

Other (OTH) AF: 0.383 AC: 8992 AN: 23468

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

African (AFR) AF: 0.662 AC: 27456 AN: 41484

American (AMR) AF: 0.465 AC: 7110 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1123 AN: 3472

East Asian (EAS) AF: 0.459 AC: 2360 AN: 5144

South Asian (SAS) AF: 0.310 AC: 1497 AN: 4826

European-Finnish (FIN) AF: 0.431 AC: 4556 AN: 10564

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.368 AC: 25014 AN: 67988

Other (OTH) AF: 0.417 AC: 881 AN: 2112

Alfa AF: 0.391 Hom.: 26779

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.7
DANN	Benign	0.80
PhyloP100		0.83
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs597320; hg19: chr11-134019361;