rs1160685381
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_203446.3(SYNJ1):c.3588G>A(p.Pro1196=) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.00000137 in 1,456,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_203446.3 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 |
---|---|---|---|---|---|---|---|
SYNJ1 | NM_203446.3 | c.3588G>A | p.Pro1196= | splice_region_variant, synonymous_variant | 29/33 | ENST00000674351.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNJ1 | ENST00000674351.1 | c.3588G>A | p.Pro1196= | splice_region_variant, synonymous_variant | 29/33 | NM_203446.3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1456408Hom.: 0 Cov.: 32 AF XY: 0.00000276 AC XY: 2AN XY: 724410
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Early-onset Parkinson disease 20;C4479313:Developmental and epileptic encephalopathy, 53 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 10, 2023 | This sequence change affects codon 1235 of the SYNJ1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the SYNJ1 protein. This variant also falls at the last nucleotide of exon 29, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SYNJ1-related conditions. ClinVar contains an entry for this variant (Variation ID: 478344). 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. 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