11-134127758-C-T

Variant names:

• chr11-134127758-C-T
• rs470719
• NM_032801.5:c.77-12093C>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.77-12093C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0309 in 152,294 control chromosomes in the GnomAD database, including 257 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 0.031 (257 hom., cov: 33)
• Consequence: JAM3 NM_032801.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320
• Publications: 1 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JAM3	NM_032801.5	c.77-12093C>T		intron_variant	Intron 1 of 8	ENST00000299106.9	NP_116190.3
JAM3	NM_001205329.2	c.77-12093C>T		intron_variant	Intron 1 of 7		NP_001192258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JAM3	ENST00000299106.9	c.77-12093C>T		intron_variant	Intron 1 of 8	1	NM_032801.5	ENSP00000299106.4

Frequencies

GnomAD3 genomes AF: 0.0309 AC: 4706 AN: 152176 Hom.: 261 Cov.: 33

Gnomad AFR AF: 0.0240

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0332

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0139

Gnomad OTH AF: 0.0273

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

GnomAD4 genome AF: 0.0309 AC: 4708 AN: 152294 Hom.: 257 Cov.: 33 AF XY: 0.0342 AC XY: 2544 AN XY: 74458

African (AFR) AF: 0.0241 AC: 1002 AN: 41578

American (AMR) AF: 0.0144 AC: 220 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0323 AC: 112 AN: 3470

East Asian (EAS) AF: 0.254 AC: 1315 AN: 5180

South Asian (SAS) AF: 0.144 AC: 694 AN: 4824

European-Finnish (FIN) AF: 0.0332 AC: 352 AN: 10608

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0139 AC: 944 AN: 68022

Other (OTH) AF: 0.0294 AC: 62 AN: 2112

Alfa AF: 0.0225 Hom.: 8

Bravo AF: 0.0270

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.2
DANN	Benign	0.76
PhyloP100		-0.032
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: rs470719; hg19: chr11-133997653;