rs774867496

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePS1_ModeratePM2

The NM_032801.5(JAM3):ā€‹c.1A>Cā€‹(p.Met1?) variant causes a initiator codon change. The variant allele was found at a frequency of 0.00000411 in 1,458,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000041 ( 0 hom. )

Consequence

JAM3
NM_032801.5 initiator_codon

Scores

3
6
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.26
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PVS1
Start lost variant, next in-frame start position is after 2 pathogenic variants. Next in-frame start position is after 462 CDS bases. Genomic position: 134144844. Lost 0.495 part of the original CDS.
PS1
Another start lost variant in NM_032801.5 (JAM3) was described as [Pathogenic] in Lovd
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
JAM3NM_032801.5 linkc.1A>C p.Met1? initiator_codon_variant Exon 1 of 9 ENST00000299106.9 NP_116190.3 Q9BX67-1
JAM3NM_001205329.2 linkc.1A>C p.Met1? initiator_codon_variant Exon 1 of 8 NP_001192258.1 Q9BX67-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
JAM3ENST00000299106.9 linkc.1A>C p.Met1? initiator_codon_variant Exon 1 of 9 1 NM_032801.5 ENSP00000299106.4 Q9BX67-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000419
AC:
1
AN:
238948
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
131146
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000941
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000411
AC:
6
AN:
1458442
Hom.:
0
Cov.:
31
AF XY:
0.00000276
AC XY:
2
AN XY:
725636
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Uncertain
0.12
CADD
Benign
21
DANN
Benign
0.88
DEOGEN2
Benign
0.093
T;T;.
Eigen
Uncertain
0.29
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.90
D;D;D
M_CAP
Pathogenic
1.0
D
MetaRNN
Pathogenic
0.77
D;D;D
MetaSVM
Benign
-0.33
T
PROVEAN
Benign
-0.50
N;N;N
REVEL
Uncertain
0.48
Sift
Benign
0.31
T;D;T
Sift4G
Benign
0.59
T;D;T
Polyphen
0.70
P;.;.
Vest4
0.89
MutPred
0.59
Gain of stability (P = 0.0591);Gain of stability (P = 0.0591);Gain of stability (P = 0.0591);
MVP
0.76
ClinPred
0.98
D
GERP RS
5.2
Varity_R
0.47
gMVP
0.64

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs774867496; hg19: chr11-133938979; API