rs191293931
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4BP6BS1BS2
The ENST00000287766.10(SLC6A1):c.1250G>A(p.Arg417His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000124 in 1,612,672 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R417C) has been classified as Likely benign.
Frequency
Consequence
ENST00000287766.10 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC6A1 | NM_003042.4 | c.1250G>A | p.Arg417His | missense_variant | 12/16 | ENST00000287766.10 | NP_003033.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC6A1 | ENST00000287766.10 | c.1250G>A | p.Arg417His | missense_variant | 12/16 | 1 | NM_003042.4 | ENSP00000287766 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000276 AC: 42AN: 152134Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.0000966 AC: 24AN: 248484Hom.: 0 AF XY: 0.000112 AC XY: 15AN XY: 134198
GnomAD4 exome AF: 0.000108 AC: 158AN: 1460420Hom.: 1 Cov.: 32 AF XY: 0.000117 AC XY: 85AN XY: 726308
GnomAD4 genome AF: 0.000276 AC: 42AN: 152252Hom.: 2 Cov.: 32 AF XY: 0.000282 AC XY: 21AN XY: 74446
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:2
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2022 | SLC6A1: PP2, BS1, BS2 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 29, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 25, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 14, 2018 | - - |
Myoclonic-astatic epilepsy Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | New York Genome Center | Jul 16, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Mar 30, 2021 | SLC6A1 NM_003042.3 exon 12 p.Arg417His (c.1250G>A): This variant has not been reported in the literature but is present in 0.02% (9/34294) of Latino alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/3-11070965-G-A). This variant is present in ClinVar (Variation ID:475469). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
SLC6A1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 16, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 28, 2019 | 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. - |
Myoclonic-atonic epilepsy Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 19, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at