10-49611297-G-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_003055.3(SLC18A3):āc.557G>Cā(p.Gly186Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_003055.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 35
GnomAD4 exome AF: 6.87e-7 AC: 1AN: 1456228Hom.: 0 Cov.: 80 AF XY: 0.00000138 AC XY: 1AN XY: 724770
GnomAD4 genome Cov.: 35
ClinVar
Submissions by phenotype
Congenital myasthenic syndrome 21 Pathogenic:1Uncertain:1
The heterozygous p.Gly186Ala variant in SLC18A3 was identified by our study, in the compound heterozygous state, along with a pathogenic deletion, in an individual with autosomal recessive congenital myasthenic syndrome (PMID: 27590285). It is of note that the deletion spans across at least 5 genes including SLC18A3. The p.Gly186Ala variant has been reported pathogenic by OMIM in ClinVar (Variation ID: 372159) and was absent from large population studies. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine impact. Furthermore, although this gene has been reported in association with congenital myasthenic syndrome, it currently has moderate evidence for these associations. In summary, the clinical significance of the p.Gly186Ala variant is uncertain. -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at