rs775109362
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_006950.3(SYN1):c.506G>A(p.Arg169Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,207,753 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R169W) has been classified as Uncertain significance.
Frequency
Consequence
NM_006950.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYN1 | NM_006950.3 | c.506G>A | p.Arg169Gln | missense_variant | 3/13 | ENST00000295987.13 | |
SYN1 | NM_133499.2 | c.506G>A | p.Arg169Gln | missense_variant | 3/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYN1 | ENST00000295987.13 | c.506G>A | p.Arg169Gln | missense_variant | 3/13 | 2 | NM_006950.3 | P3 | |
SYN1 | ENST00000340666.5 | c.506G>A | p.Arg169Gln | missense_variant | 3/13 | 1 | A1 | ||
SYN1 | ENST00000639776.1 | c.167G>A | p.Arg56Gln | missense_variant | 3/6 | 3 | |||
SYN1 | ENST00000638337.1 | n.49G>A | non_coding_transcript_exon_variant | 1/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000545 AC: 6AN: 110023Hom.: 0 Cov.: 22 AF XY: 0.0000620 AC XY: 2AN XY: 32283
GnomAD3 exomes AF: 0.0000274 AC: 5AN: 182570Hom.: 0 AF XY: 0.0000447 AC XY: 3AN XY: 67148
GnomAD4 exome AF: 0.0000109 AC: 12AN: 1097730Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 4AN XY: 363104
GnomAD4 genome ? AF: 0.0000545 AC: 6AN: 110023Hom.: 0 Cov.: 22 AF XY: 0.0000620 AC XY: 2AN XY: 32283
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 05, 2014 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 01, 2024 | The c.506G>A (p.R169Q) alteration is located in exon 3 (coding exon 3) of the SYN1 gene. This alteration results from a G to A substitution at nucleotide position 506, causing the arginine (R) at amino acid position 169 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Epilepsy, X-linked 1, with variable learning disabilities and behavior disorders Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 10, 2023 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 169 of the SYN1 protein (p.Arg169Gln). This variant is present in population databases (rs775109362, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with SYN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 212332). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2023 | SYN1: BS2 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at