rs774867496
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePS1_ModeratePM2
The NM_032801.5(JAM3):āc.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
NM_032801.5 initiator_codon
Scores
3
6
7
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 4.26
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]
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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
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.00000419 AC: 1AN: 238948Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 131146
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1458442Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2AN XY: 725636
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GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Uncertain
Sift
Benign
T;D;T
Sift4G
Benign
T;D;T
Polyphen
P;.;.
Vest4
MutPred
Gain of stability (P = 0.0591);Gain of stability (P = 0.0591);Gain of stability (P = 0.0591);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at