rs750843353
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001044.5(SLC6A3):c.1087G>A(p.Val363Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,612,738 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V363L) has been classified as Uncertain significance.
Frequency
Consequence
NM_001044.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC6A3 | NM_001044.5 | c.1087G>A | p.Val363Ile | missense_variant | 8/15 | ENST00000270349.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC6A3 | ENST00000270349.12 | c.1087G>A | p.Val363Ile | missense_variant | 8/15 | 1 | NM_001044.5 | P1 | |
SLC6A3 | ENST00000511750.1 | n.537G>A | non_coding_transcript_exon_variant | 2/2 | 4 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152050Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250716Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135794
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1460688Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 726632
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152050Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74264
ClinVar
Submissions by phenotype
Parkinsonism-dystonia, infantile Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2021 | This sequence change replaces valine with isoleucine at codon 363 of the SLC6A3 protein (p.Val363Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs750843353, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with SLC6A3-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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