rs149444784
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001044.5(SLC6A3):c.605C>T(p.Ser202Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,614,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001044.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC6A3 | NM_001044.5 | c.605C>T | p.Ser202Leu | missense_variant | 4/15 | ENST00000270349.12 | NP_001035.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC6A3 | ENST00000270349.12 | c.605C>T | p.Ser202Leu | missense_variant | 4/15 | 1 | NM_001044.5 | ENSP00000270349.9 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152232Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251440Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135906
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461866Hom.: 0 Cov.: 33 AF XY: 0.0000124 AC XY: 9AN XY: 727242
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152350Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74504
ClinVar
Submissions by phenotype
Parkinsonism-dystonia, infantile Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 15, 2021 | 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SLC6A3-related disease. This variant is present in population databases (rs149444784, ExAC 0.003%). This sequence change replaces serine with leucine at codon 202 of the SLC6A3 protein (p.Ser202Leu). The serine residue is weakly conserved and there is a large physicochemical difference between serine and leucine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at