11-134085430-A-G

Variant names:

• chr11-134085430-A-G
• rs647837
• NM_032801.5:c.76+16271A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032801.5(JAM3):​c.76+16271A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,256 control chromosomes in the GnomAD database, including 1,276 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 0.11 (1276 hom., cov: 33)
• Consequence: JAM3 NM_032801.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64
• Publications: 7 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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032801.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAM3	NM_032801.5	MANE Select	c.76+16271A>G		intron	N/A	NP_116190.3
	JAM3	NM_001205329.2		c.76+16271A>G		intron	N/A	NP_001192258.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAM3	ENST00000299106.9	TSL:1 MANE Select	c.76+16271A>G		intron	N/A	ENSP00000299106.4
	JAM3	ENST00000441717.3	TSL:2	c.76+16271A>G		intron	N/A	ENSP00000395742.3
	JAM3	ENST00000534549.5	TSL:4	c.76+16271A>G		intron	N/A	ENSP00000433206.1

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17467 AN: 152138 Hom.: 1280 Cov.: 33

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0643

Gnomad ASJ AF: 0.0968

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0724

Gnomad OTH AF: 0.101

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.115 AC: 17475 AN: 152256 Hom.: 1276 Cov.: 33 AF XY: 0.118 AC XY: 8819 AN XY: 74434

African (AFR) AF: 0.170 AC: 7078 AN: 41538

American (AMR) AF: 0.0642 AC: 982 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0968 AC: 336 AN: 3472

East Asian (EAS) AF: 0.299 AC: 1552 AN: 5182

South Asian (SAS) AF: 0.155 AC: 746 AN: 4828

European-Finnish (FIN) AF: 0.153 AC: 1617 AN: 10600

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0724 AC: 4925 AN: 68016

Other (OTH) AF: 0.103 AC: 217 AN: 2114

Alfa AF: 0.102 Hom.: 344

Bravo AF: 0.110

Asia WGS AF: 0.212 AC: 734 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	13
DANN	Benign	0.91
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs647837; hg19: chr11-133955325;