rs140606359
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP3BS1_Supporting
The NM_002230.4(JUP):c.926A>T(p.Asn309Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,613,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N309S) has been classified as Likely benign.
Frequency
Consequence
NM_002230.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
JUP | NM_002230.4 | c.926A>T | p.Asn309Ile | missense_variant | 6/14 | ENST00000393931.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
JUP | ENST00000393931.8 | c.926A>T | p.Asn309Ile | missense_variant | 6/14 | 1 | NM_002230.4 | P1 | |
JUP | ENST00000310706.9 | c.926A>T | p.Asn309Ile | missense_variant | 6/15 | 1 | P1 | ||
JUP | ENST00000393930.5 | c.926A>T | p.Asn309Ile | missense_variant | 6/15 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152156Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251420Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135890
GnomAD4 exome AF: 0.0000239 AC: 35AN: 1461802Hom.: 0 Cov.: 32 AF XY: 0.0000371 AC XY: 27AN XY: 727206
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152156Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74334
ClinVar
Submissions by phenotype
Naxos disease;C1969081:Arrhythmogenic right ventricular dysplasia 12 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 10, 2018 | This sequence change replaces asparagine with isoleucine at codon 309 of the JUP protein (p.Asn309Ile). The asparagine residue is moderately conserved and there is a large physicochemical difference between asparagine and isoleucine. This variant is present in population databases (rs140606359, ExAC 0.04%). This variant has not been reported in the literature in individuals with JUP-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at