11-134142118-G-A

Variant names:

• chr11-134142118-G-A
• rs10791345
• NM_032801.5:c.256+1348G>A

Variant summary

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

The NM_032801.5(JAM3):​c.256+1348G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,054 control chromosomes in the GnomAD database, including 2,466 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 0.18 (2466 hom., cov: 32)
• Consequence: JAM3 NM_032801.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.847
• Publications: 6 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JAM3	NM_032801.5	c.256+1348G>A		intron_variant	Intron 3 of 8	ENST00000299106.9	NP_116190.3
JAM3	NM_001205329.2	c.256+1348G>A		intron_variant	Intron 3 of 7		NP_001192258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JAM3	ENST00000299106.9	c.256+1348G>A		intron_variant	Intron 3 of 8	1	NM_032801.5	ENSP00000299106.4

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26734 AN: 151936 Hom.: 2458 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.0754

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.176 AC: 26768 AN: 152054 Hom.: 2466 Cov.: 32 AF XY: 0.179 AC XY: 13269 AN XY: 74320

African (AFR) AF: 0.212 AC: 8776 AN: 41442

American (AMR) AF: 0.164 AC: 2515 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 419 AN: 3468

East Asian (EAS) AF: 0.142 AC: 732 AN: 5150

South Asian (SAS) AF: 0.0765 AC: 368 AN: 4812

European-Finnish (FIN) AF: 0.243 AC: 2570 AN: 10578

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10922 AN: 68000

Other (OTH) AF: 0.151 AC: 318 AN: 2110

Alfa AF: 0.160 Hom.: 1089

Bravo AF: 0.173

Asia WGS AF: 0.0980 AC: 341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	12
DANN	Benign	0.54
PhyloP100		0.85
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs10791345; hg19: chr11-134012013;