rs201117151
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_203446.3(SYNJ1):c.3762C>T(p.Pro1254=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,613,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 0 hom. )
Consequence
SYNJ1
NM_203446.3 synonymous
NM_203446.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.183
Genes affected
SYNJ1 (HGNC:11503): (synaptojanin 1) This gene encodes a phosphoinositide phosphatase that regulates levels of membrane phosphatidylinositol-4,5-bisphosphate. As such, expression of this enzyme may affect synaptic transmission and membrane trafficking. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 21-32639061-G-A is Benign according to our data. Variant chr21-32639061-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 478351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-32639061-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-0.183 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNJ1 | NM_203446.3 | c.3762C>T | p.Pro1254= | synonymous_variant | 31/33 | ENST00000674351.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNJ1 | ENST00000674351.1 | c.3762C>T | p.Pro1254= | synonymous_variant | 31/33 | NM_203446.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000855 AC: 13AN: 152122Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000835 AC: 21AN: 251466Hom.: 0 AF XY: 0.0000957 AC XY: 13AN XY: 135908
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GnomAD4 exome AF: 0.000134 AC: 196AN: 1461826Hom.: 0 Cov.: 30 AF XY: 0.000139 AC XY: 101AN XY: 727208
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GnomAD4 genome ? AF: 0.0000855 AC: 13AN: 152122Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74310
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Early-onset Parkinson disease 20;C4479313:Developmental and epileptic encephalopathy, 53 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 18, 2023 | - - |
SYNJ1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 12, 2019 | 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). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | SYNJ1: BP4, BP7 - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at