NM_032801.5:c.76+253C>T

Variant names:

• chr11-134069412-C-T
• rs144554045
• NM_032801.5:c.76+253C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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: Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAM3	NM_032801.5	MANE Select	c.76+253C>T		intron	N/A	NP_116190.3
	JAM3	NM_001205329.2		c.76+253C>T		intron	N/A	NP_001192258.1	Q9BX67-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAM3	ENST00000299106.9	TSL:1 MANE Select	c.76+253C>T		intron	N/A	ENSP00000299106.4	Q9BX67-1
	JAM3	ENST00000963685.1		c.76+253C>T		intron	N/A	ENSP00000633744.1
	JAM3	ENST00000876942.1		c.76+253C>T		intron	N/A	ENSP00000547001.1

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

African (AFR) AF: 0.0270 AC: 1121 AN: 41546

American (AMR) AF: 0.0467 AC: 712 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 352 AN: 3456

East Asian (EAS) AF: 0.000389 AC: 2 AN: 5140

South Asian (SAS) AF: 0.0384 AC: 185 AN: 4820

European-Finnish (FIN) AF: 0.0555 AC: 587 AN: 10580

Middle Eastern (MID) AF: 0.0724 AC: 21 AN: 290

European-Non Finnish (NFE) AF: 0.0840 AC: 5691 AN: 67712

Other (OTH) AF: 0.0630 AC: 133 AN: 2112

Alfa AF: 0.0687 Hom.: 47

Bravo AF: 0.0579

Asia WGS AF: 0.0160 AC: 55 AN: 3470

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.6
DANN	Benign	0.86
PhyloP100		0.73
PromoterAI		-0.059	Neutral
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: rs144554045; hg19: chr11-133939307;