chrX-47574036-C-CGGTGGCG
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePM2PP5_Moderate
The NM_006950.3(SYN1):c.1947_1948insCGCCACC(p.Ala650ArgfsTer36) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. T649T) has been classified as Likely benign.
Frequency
Consequence
NM_006950.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYN1 | NM_006950.3 | c.1947_1948insCGCCACC | p.Ala650ArgfsTer36 | frameshift_variant | 12/13 | ENST00000295987.13 | |
SYN1 | NM_133499.2 | c.1947_1948insCGCCACC | p.Ala650ArgfsTer28 | frameshift_variant | 12/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYN1 | ENST00000295987.13 | c.1947_1948insCGCCACC | p.Ala650ArgfsTer36 | frameshift_variant | 12/13 | 2 | NM_006950.3 | P3 | |
SYN1 | ENST00000340666.5 | c.1947_1948insCGCCACC | p.Ala650ArgfsTer28 | frameshift_variant | 12/13 | 1 | A1 | ||
SYN1 | ENST00000640721.1 | c.70+651_70+652insCGCCACC | intron_variant | 5 |
Frequencies
GnomAD3 genomes Cov.: 24
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 24
ClinVar
Submissions by phenotype
Epilepsy, X-linked 1, with variable learning disabilities and behavior disorders Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 03, 2023 | This sequence change results in a frameshift in the SYN1 gene (p.Ala650Argfs*28). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 20 amino acid(s) of the SYN1 protein and extend the protein by 7 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This frameshift has been observed in individual(s) with early onset epilepsy (Invitae). ClinVar contains an entry for this variant (Variation ID: 1067772). This variant disrupts a region of the SYN1 protein in which other variant(s) (p.Pro664Ser) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.