rs147544792
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_203446.3(SYNJ1):c.1106G>A(p.Ser369Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0001 in 1,605,498 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_203446.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNJ1 | NM_203446.3 | c.1106G>A | p.Ser369Asn | missense_variant | 9/33 | ENST00000674351.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNJ1 | ENST00000674351.1 | c.1106G>A | p.Ser369Asn | missense_variant | 9/33 | NM_203446.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152082Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000733 AC: 18AN: 245486Hom.: 0 AF XY: 0.0000753 AC XY: 10AN XY: 132854
GnomAD4 exome AF: 0.000103 AC: 150AN: 1453416Hom.: 0 Cov.: 30 AF XY: 0.0000954 AC XY: 69AN XY: 722902
GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152082Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74312
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 24, 2022 | The c.1223G>A (p.S408N) alteration is located in exon 9 (coding exon 9) of the SYNJ1 gene. This alteration results from a G to A substitution at nucleotide position 1223, causing the serine (S) at amino acid position 408 to be replaced by an asparagine (N). 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 | Aug 16, 2022 | This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 408 of the SYNJ1 protein (p.Ser408Asn). This variant is present in population databases (rs147544792, gnomAD 0.01%). 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: 582650). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | SYNJ1: PM2, BP4 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at