chr11-134069360-C-T

Variant names:

• chr11-134069360-C-T
• rs149286072
• NM_032801.5:c.76+201C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_032801.5(JAM3):​c.76+201C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 152,186 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.010 (24 hom., cov: 33)
• Consequence: JAM3 NM_032801.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.808
• Publications: 0 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=-0.83).
• BP6: Variant 11-134069360-C-T is Benign according to our data. Variant chr11-134069360-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1217180.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0101 (1531/152186) while in subpopulation AFR AF = 0.0346 (1438/41544). AF 95% confidence interval is 0.0331. There are 24 homozygotes in GnomAd4. There are 727 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 24 AR gene

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+201C>T		intron	N/A	NP_116190.3
	JAM3	NM_001205329.2		c.76+201C>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+201C>T		intron	N/A	ENSP00000299106.4	Q9BX67-1
	JAM3	ENST00000963685.1		c.76+201C>T		intron	N/A	ENSP00000633744.1
	JAM3	ENST00000876942.1		c.76+201C>T		intron	N/A	ENSP00000547001.1

Frequencies

GnomAD3 genomes AF: 0.0100 AC: 1524 AN: 152076 Hom.: 23 Cov.: 33

Gnomad AFR AF: 0.0345

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00380

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0105

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

GnomAD4 genome AF: 0.0101 AC: 1531 AN: 152186 Hom.: 24 Cov.: 33 AF XY: 0.00977 AC XY: 727 AN XY: 74418

African (AFR) AF: 0.0346 AC: 1438 AN: 41544

American (AMR) AF: 0.00379 AC: 58 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5140

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67986

Other (OTH) AF: 0.0104 AC: 22 AN: 2114

Alfa AF: 0.00862 Hom.: 2

Bravo AF: 0.0111

Asia WGS AF: 0.00174 AC: 6 AN: 3470

ClinVar

ClinVar submissions

Significance: Likely 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	-0.83
CADD	Benign	5.2
DANN	Benign	0.81
PhyloP100		-0.81
PromoterAI		0.078	Neutral
Mutation Taster		=100/0	polymorphism

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: rs149286072; hg19: chr11-133939255;