10-49610774-GC-AG
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.
The NM_003055.3(SLC18A3):c.34_35delGCinsAG(p.Ala12Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. The variant is present in control chromosomes in GnomAd MNV project. The variant allele was found at a frequency of 0.0000637 in 2 alleles, including 0 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A12A) has been classified as Likely benign.
Frequency
Consequence
NM_003055.3 missense
Scores
Clinical Significance
Conservation
Publications
- congenital myasthenic syndrome 6Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
- presynaptic congenital myasthenic syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC18A3 | ENST00000374115.5 | c.34_35delGCinsAG | p.Ala12Arg | missense_variant | 6 | NM_003055.3 | ENSP00000363229.3 | |||
CHAT | ENST00000339797.5 | c.-69+1575_-69+1576delGCinsAG | intron_variant | Intron 1 of 14 | 1 | ENSP00000343486.1 |
Frequencies
GnomAD3 genomes Cov.: 35
GnomAD4 genome Cov.: 35
ClinVar
Submissions by phenotype
not provided Uncertain:1
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. 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: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). This variant has not been reported in the literature in individuals affected with SLC18A3-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces alanine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 12 of the SLC18A3 protein (p.Ala12Arg). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at