rs770195822
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_006950.3(SYN1):c.1701A>T(p.Thr567=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000272 in 1,102,205 control chromosomes in the GnomAD database, including 1 homozygotes. There are 92 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00044 ( 0 hom., 17 hem., cov: 23)
Exomes 𝑓: 0.00025 ( 1 hom. 75 hem. )
Consequence
SYN1
NM_006950.3 synonymous
NM_006950.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.364
Genes affected
SYN1 (HGNC:11494): (synapsin I) This gene is a member of the synapsin gene family. Synapsins encode neuronal phosphoproteins which associate with the cytoplasmic surface of synaptic vesicles. Family members are characterized by common protein domains, and they are implicated in synaptogenesis and the modulation of neurotransmitter release, suggesting a potential role in several neuropsychiatric diseases. This member of the synapsin family plays a role in regulation of axonogenesis and synaptogenesis. The protein encoded serves as a substrate for several different protein kinases and phosphorylation may function in the regulation of this protein in the nerve terminal. Mutations in this gene may be associated with X-linked disorders with primary neuronal degeneration such as Rett syndrome. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
?
Variant X-47574283-T-A is Benign according to our data. Variant chrX-47574283-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 465092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.364 with no splicing effect.
BS2
?
High Hemizygotes in GnomAd at 17 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYN1 | NM_006950.3 | c.1701A>T | p.Thr567= | synonymous_variant | 12/13 | ENST00000295987.13 | |
SYN1 | NM_133499.2 | c.1701A>T | p.Thr567= | synonymous_variant | 12/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYN1 | ENST00000295987.13 | c.1701A>T | p.Thr567= | synonymous_variant | 12/13 | 2 | NM_006950.3 | P3 | |
SYN1 | ENST00000340666.5 | c.1701A>T | p.Thr567= | synonymous_variant | 12/13 | 1 | A1 | ||
SYN1 | ENST00000640721.1 | c.70+405A>T | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000438 AC: 49AN: 111773Hom.: 0 Cov.: 23 AF XY: 0.000497 AC XY: 17AN XY: 34237
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GnomAD3 exomes AF: 0.000222 AC: 12AN: 54143Hom.: 0 AF XY: 0.0000538 AC XY: 1AN XY: 18581
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GnomAD4 exome AF: 0.000253 AC: 251AN: 990432Hom.: 1 Cov.: 32 AF XY: 0.000235 AC XY: 75AN XY: 319216
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ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 13, 2018 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
SYN1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 29, 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 | May 01, 2023 | SYN1: BP4, BP7, BS2 - |
Epilepsy, X-linked 1, with variable learning disabilities and behavior disorders Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 09, 2024 | - - |
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