rs145937537
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_203446.3(SYNJ1):c.3590C>T(p.Thr1197Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00195 in 1,612,648 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T1197T) has been classified as Likely benign.
Frequency
Consequence
NM_203446.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNJ1 | NM_203446.3 | c.3590C>T | p.Thr1197Met | missense_variant, splice_region_variant | 30/33 | ENST00000674351.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNJ1 | ENST00000674351.1 | c.3590C>T | p.Thr1197Met | missense_variant, splice_region_variant | 30/33 | NM_203446.3 |
Frequencies
GnomAD3 genomes ? AF: 0.00193 AC: 293AN: 152160Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.00148 AC: 371AN: 250702Hom.: 1 AF XY: 0.00139 AC XY: 189AN XY: 135502
GnomAD4 exome AF: 0.00196 AC: 2857AN: 1460370Hom.: 5 Cov.: 29 AF XY: 0.00185 AC XY: 1346AN XY: 726622
GnomAD4 genome ? AF: 0.00193 AC: 294AN: 152278Hom.: 2 Cov.: 32 AF XY: 0.00172 AC XY: 128AN XY: 74460
ClinVar
Submissions by phenotype
not provided Benign:5
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 01, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 03, 2020 | This variant is associated with the following publications: (PMID: 27393345) - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | SYNJ1: BS2 - |
Early-onset Parkinson disease 20;C4479313:Developmental and epileptic encephalopathy, 53 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
SYNJ1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 04, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at