rs114053718
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting
The NM_203446.3(SYNJ1):āc.2597T>Cā(p.Ile866Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000812 in 1,614,186 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I866V) has been classified as Uncertain significance.
Frequency
Consequence
NM_203446.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNJ1 | NM_203446.3 | c.2597T>C | p.Ile866Thr | missense_variant | 21/33 | ENST00000674351.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNJ1 | ENST00000674351.1 | c.2597T>C | p.Ile866Thr | missense_variant | 21/33 | NM_203446.3 |
Frequencies
GnomAD3 genomes AF: 0.000177 AC: 27AN: 152246Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000127 AC: 32AN: 251016Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135800
GnomAD4 exome AF: 0.0000705 AC: 103AN: 1461822Hom.: 1 Cov.: 31 AF XY: 0.0000660 AC XY: 48AN XY: 727204
GnomAD4 genome AF: 0.000184 AC: 28AN: 152364Hom.: 0 Cov.: 33 AF XY: 0.000255 AC XY: 19AN XY: 74512
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 02, 2021 | The c.2714T>C (p.I905T) alteration is located in exon 21 (coding exon 21) of the SYNJ1 gene. This alteration results from a T to C substitution at nucleotide position 2714, causing the isoleucine (I) at amino acid position 905 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Early-onset Parkinson disease 20;C4479313:Developmental and epileptic encephalopathy, 53 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 12, 2022 | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 905 of the SYNJ1 protein (p.Ile905Thr). This variant is present in population databases (rs114053718, gnomAD 0.07%). 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: 544554). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SYNJ1 protein function. 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