rs1238065971
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_203446.3(SYNJ1):āc.1466T>Cā(p.Leu489Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,459,548 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L489V) has been classified as Uncertain significance.
Frequency
Consequence
NM_203446.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNJ1 | NM_203446.3 | c.1466T>C | p.Leu489Ser | missense_variant | 12/33 | ENST00000674351.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNJ1 | ENST00000674351.1 | c.1466T>C | p.Leu489Ser | missense_variant | 12/33 | NM_203446.3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000405 AC: 1AN: 246650Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 133472
GnomAD4 exome AF: 0.00000548 AC: 8AN: 1459548Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 726052
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 | Sep 18, 2017 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with SYNJ1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with serine at codon 528 of the SYNJ1 protein (p.Leu528Ser). The leucine residue is highly conserved and there is a large physicochemical difference between leucine and serine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at