11-134127758-C-T

Position:

• chr11-134127758-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	Protein	UniProt
JAM3	NM_032801.5	c.77-12093C>T		intron_variant		ENST00000299106.9	NP_116190.3
JAM3	NM_001205329.2	c.77-12093C>T		intron_variant			NP_001192258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JAM3	ENST00000299106.9	c.77-12093C>T		intron_variant		1	NM_032801.5	ENSP00000299106	P1

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

Gnomad4 AFR AF: 0.0241

Gnomad4 AMR AF: 0.0144

Gnomad4 ASJ AF: 0.0323

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.0332

Gnomad4 NFE AF: 0.0139

Gnomad4 OTH AF: 0.0294

Alfa AF: 0.0223 Hom.: 7

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs470719; hg19: chr11-133997653;