15-29701654-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001330239.4(TJP1):c.5248G>A(p.Gly1750Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,613,804 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
TJP1
NM_001330239.4 missense
NM_001330239.4 missense
Scores
7
8
4
Clinical Significance
Conservation
PhyloP100: 6.14
Genes affected
TJP1 (HGNC:11827): (tight junction protein 1) This gene encodes a member of the membrane-associated guanylate kinase (MAGUK) family of proteins, and acts as a tight junction adaptor protein that also regulates adherens junctions. Tight junctions regulate the movement of ions and macromolecules between endothelial and epithelial cells. The multidomain structure of this scaffold protein, including a postsynaptic density 95/disc-large/zona occludens (PDZ) domain, a Src homology (SH3) domain, a guanylate kinase (GuK) domain and unique (U) motifs all help to co-ordinate binding of transmembrane proteins, cytosolic proteins, and F-actin, which are required for tight junction function. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TJP1 | NM_001330239.4 | c.5248G>A | p.Gly1750Arg | missense_variant | 28/28 | ENST00000614355.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TJP1 | ENST00000614355.5 | c.5248G>A | p.Gly1750Arg | missense_variant | 28/28 | 5 | NM_001330239.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152038Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249366Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135310
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461766Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 727184
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GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152038Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74238
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 23, 2024 | The c.5188G>A (p.G1730R) alteration is located in exon 28 (coding exon 28) of the TJP1 gene. This alteration results from a G to A substitution at nucleotide position 5188, causing the glycine (G) at amino acid position 1730 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Uncertain
D;T;.;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D;.;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;.;D
Sift4G
Uncertain
D;D;D;D;D
Polyphen
D;D;.;.;D
Vest4
MutPred
Gain of solvent accessibility (P = 0.0042);.;.;.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
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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