rs782044013
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_002230.4(JUP):c.1653G>T(p.Thr551=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T551T) has been classified as Uncertain significance.
Frequency
Consequence
NM_002230.4 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
JUP | NM_002230.4 | c.1653G>T | p.Thr551= | splice_region_variant, synonymous_variant | 9/14 | ENST00000393931.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
JUP | ENST00000393931.8 | c.1653G>T | p.Thr551= | splice_region_variant, synonymous_variant | 9/14 | 1 | NM_002230.4 | P1 | |
JUP | ENST00000310706.9 | c.1653G>T | p.Thr551= | splice_region_variant, synonymous_variant | 9/15 | 1 | P1 | ||
JUP | ENST00000393930.5 | c.1653G>T | p.Thr551= | splice_region_variant, synonymous_variant | 9/15 | 5 | P1 | ||
JUP | ENST00000585793.1 | n.251G>T | splice_region_variant, non_coding_transcript_exon_variant | 2/3 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1446714Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 718500
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Naxos disease;C1969081:Arrhythmogenic right ventricular dysplasia 12 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 20, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant has not been reported in the literature in individuals affected with JUP-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects codon 551 of the JUP mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the JUP protein. This variant also falls at the last nucleotide of exon 9, which is part of the consensus splice site for this exon. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at