rs145114326
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_001044.5(SLC6A3):c.1155C>T(p.Asp385=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000434 in 1,612,378 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001044.5 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC6A3 | NM_001044.5 | c.1155C>T | p.Asp385= | splice_region_variant, synonymous_variant | 8/15 | ENST00000270349.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC6A3 | ENST00000270349.12 | c.1155C>T | p.Asp385= | splice_region_variant, synonymous_variant | 8/15 | 1 | NM_001044.5 | P1 | |
SLC6A3 | ENST00000511750.1 | downstream_gene_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.000434 AC: 66AN: 152064Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000493 AC: 123AN: 249568Hom.: 0 AF XY: 0.000414 AC XY: 56AN XY: 135402
GnomAD4 exome AF: 0.000433 AC: 632AN: 1460196Hom.: 2 Cov.: 32 AF XY: 0.000434 AC XY: 315AN XY: 726408
GnomAD4 genome ? AF: 0.000440 AC: 67AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.000484 AC XY: 36AN XY: 74406
ClinVar
Submissions by phenotype
Tobacco addiction, susceptibility to;C5700336:Classic dopamine transporter deficiency syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 21, 2021 | - - |
Parkinsonism-dystonia, infantile Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2022 | This sequence change affects codon 385 of the SLC6A3 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the SLC6A3 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs145114326, gnomAD 0.09%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with SLC6A3-related conditions. ClinVar contains an entry for this variant (Variation ID: 538065). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 30, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2022 | SLC6A3: BP4, BP7 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at