rs377385507
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_006950.3(SYN1):c.1056-14_1056-8del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,200,263 control chromosomes in the GnomAD database, including 11 homozygotes. There are 385 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0057 ( 3 hom., 174 hem., cov: 23)
Exomes 𝑓: 0.00070 ( 8 hom. 211 hem. )
Consequence
SYN1
NM_006950.3 splice_region, splice_polypyrimidine_tract, intron
NM_006950.3 splice_region, splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.09
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 -16 ACMG points.
BP6
?
Variant X-47576240-AGACAAAG-A is Benign according to our data. Variant chrX-47576240-AGACAAAG-A is described in ClinVar as [Benign]. Clinvar id is 199183.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-47576240-AGACAAAG-A is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00574 (646/112452) while in subpopulation AFR AF= 0.0194 (600/30967). AF 95% confidence interval is 0.0181. There are 3 homozygotes in gnomad4. There are 174 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 3 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYN1 | NM_006950.3 | c.1056-14_1056-8del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000295987.13 | |||
SYN1 | NM_133499.2 | c.1056-14_1056-8del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYN1 | ENST00000295987.13 | c.1056-14_1056-8del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 2 | NM_006950.3 | P3 | |||
SYN1 | ENST00000340666.5 | c.1056-14_1056-8del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00569 AC: 640AN: 112397Hom.: 3 Cov.: 23 AF XY: 0.00489 AC XY: 169AN XY: 34545
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GnomAD3 exomes AF: 0.00176 AC: 281AN: 159843Hom.: 5 AF XY: 0.00107 AC XY: 53AN XY: 49683
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GnomAD4 exome AF: 0.000700 AC: 762AN: 1087811Hom.: 8 AF XY: 0.000594 AC XY: 211AN XY: 355325
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GnomAD4 genome ? AF: 0.00574 AC: 646AN: 112452Hom.: 3 Cov.: 23 AF XY: 0.00503 AC XY: 174AN XY: 34610
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 30, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 16, 2015 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
SYN1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 09, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 11, 2017 | - - |
Epilepsy, X-linked 1, with variable learning disabilities and behavior disorders Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at