rs757417973
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_ModerateBP6BS1
The NM_001044.5(SLC6A3):c.77C>T(p.Pro26Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,614,062 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P26P) has been classified as Likely benign.
Frequency
Consequence
NM_001044.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC6A3 | NM_001044.5 | c.77C>T | p.Pro26Leu | missense_variant | 2/15 | ENST00000270349.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC6A3 | ENST00000270349.12 | c.77C>T | p.Pro26Leu | missense_variant | 2/15 | 1 | NM_001044.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000789 AC: 12AN: 152182Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000159 AC: 40AN: 251348Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135864
GnomAD4 exome AF: 0.0000465 AC: 68AN: 1461880Hom.: 1 Cov.: 33 AF XY: 0.0000385 AC XY: 28AN XY: 727242
GnomAD4 genome ? AF: 0.0000789 AC: 12AN: 152182Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74350
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 12, 2022 | The c.77C>T (p.P26L) alteration is located in exon 2 (coding exon 1) of the SLC6A3 gene. This alteration results from a C to T substitution at nucleotide position 77, causing the proline (P) at amino acid position 26 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Parkinsonism-dystonia, infantile Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 14, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at