rs1391622247
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006950.3(SYN1):c.1967C>T(p.Pro656Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000349 in 1,146,013 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_006950.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SYN1 | ENST00000295987.13 | c.1967C>T | p.Pro656Leu | missense_variant | Exon 12 of 13 | 2 | NM_006950.3 | ENSP00000295987.7 | ||
SYN1 | ENST00000340666.5 | c.1967C>T | p.Pro656Leu | missense_variant | Exon 12 of 13 | 1 | ENSP00000343206.4 | |||
SYN1 | ENST00000640721.1 | c.70+671C>T | intron_variant | Intron 1 of 1 | 5 | ENSP00000492857.1 |
Frequencies
GnomAD3 genomes AF: 0.00000890 AC: 1AN: 112345Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 34561
GnomAD4 exome AF: 0.00000290 AC: 3AN: 1033668Hom.: 0 Cov.: 32 AF XY: 0.00000301 AC XY: 1AN XY: 332442
GnomAD4 genome AF: 0.00000890 AC: 1AN: 112345Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 34561
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.1967C>T (p.P656L) alteration is located in exon 12 (coding exon 12) of the SYN1 gene. This alteration results from a C to T substitution at nucleotide position 1967, causing the proline (P) at amino acid position 656 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function -
Epilepsy, X-linked 1, with variable learning disabilities and behavior disorders Uncertain:1
This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 656 of the SYN1 protein (p.Pro656Leu). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 1307134). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at