chr11-134069412-C-T

Position:

• chr11-134069412-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032801.5(JAM3):​c.76+253C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0591 in 151,810 control chromosomes in the GnomAD database, including 357 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.059 (357 hom., cov: 33)
• Consequence: JAM3 NM_032801.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.734

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-134069412-C-T is Benign according to our data. Variant chr11-134069412-C-T is described in ClinVar as [Benign]. Clinvar id is 1231657.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JAM3	NM_032801.5	c.76+253C>T		intron_variant		ENST00000299106.9	NP_116190.3
JAM3	NM_001205329.2	c.76+253C>T		intron_variant			NP_001192258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JAM3	ENST00000299106.9	c.76+253C>T		intron_variant		1	NM_032801.5	ENSP00000299106	P1

Frequencies

GnomAD3 genomes AF: 0.0592 AC: 8976 AN: 151702 Hom.: 357 Cov.: 33

Gnomad AFR AF: 0.0270

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.0468

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.0386

Gnomad FIN AF: 0.0555

Gnomad MID AF: 0.0673

Gnomad NFE AF: 0.0841

Gnomad OTH AF: 0.0646

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

GnomAD4 genome AF: 0.0591 AC: 8973 AN: 151810 Hom.: 357 Cov.: 33 AF XY: 0.0573 AC XY: 4250 AN XY: 74216

Gnomad4 AFR AF: 0.0270

Gnomad4 AMR AF: 0.0467

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.000389

Gnomad4 SAS AF: 0.0384

Gnomad4 FIN AF: 0.0555

Gnomad4 NFE AF: 0.0840

Gnomad4 OTH AF: 0.0630

Alfa AF: 0.0687 Hom.: 47

Bravo AF: 0.0579

Asia WGS AF: 0.0160 AC: 55 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.6
DANN	Benign	0.86

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: rs144554045; hg19: chr11-133939307;