17-41758746-T-G
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_002230.4(JUP):āc.1622A>Cā(p.His541Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000413 in 1,454,212 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0 ( 0 hom., cov: 32)
Exomes š: 0.0000041 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
JUP
NM_002230.4 missense
NM_002230.4 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 2.03
Genes affected
JUP (HGNC:6207): (junction plakoglobin) This gene encodes a major cytoplasmic protein which is the only known constituent common to submembranous plaques of both desmosomes and intermediate junctions. This protein forms distinct complexes with cadherins and desmosomal cadherins and is a member of the catenin family since it contains a distinct repeating amino acid motif called the armadillo repeat. Mutation in this gene has been associated with Naxos disease. Alternative splicing occurs in this gene; however, not all transcripts have been fully described. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
JUP | NM_002230.4 | c.1622A>C | p.His541Pro | missense_variant | 9/14 | ENST00000393931.8 | NP_002221.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
JUP | ENST00000393931.8 | c.1622A>C | p.His541Pro | missense_variant | 9/14 | 1 | NM_002230.4 | ENSP00000377508.3 | ||
JUP | ENST00000310706.9 | c.1622A>C | p.His541Pro | missense_variant | 9/15 | 1 | ENSP00000311113.5 | |||
JUP | ENST00000393930.5 | c.1622A>C | p.His541Pro | missense_variant | 9/15 | 5 | ENSP00000377507.1 | |||
JUP | ENST00000585793.1 | n.220A>C | non_coding_transcript_exon_variant | 2/3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 0AN: 152062Hom.: 0 Cov.: 32 FAILED QC
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GnomAD3 exomes AF: 0.00000427 AC: 1AN: 234452Hom.: 0 AF XY: 0.00000786 AC XY: 1AN XY: 127238
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GnomAD4 exome AF: 0.00000413 AC: 6AN: 1454212Hom.: 0 Cov.: 32 AF XY: 0.00000415 AC XY: 3AN XY: 722870
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GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 152062Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74292
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 25, 2022 | The p.H541P variant (also known as c.1622A>C), located in coding exon 8 of the JUP gene, results from an A to C substitution at nucleotide position 1622. The histidine at codon 541 is replaced by proline, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;.;T
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Benign
T;T;T
Polyphen
B;B;B
Vest4
MutPred
Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);
MVP
MPC
0.77
ClinPred
T
GERP RS
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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